1,175 results
Search Results
2. This paper is the winner of an SFB Award in the Hospital Intern, Residency category: Peptide biomaterials raising adaptive immune responses in wound healing contexts.
- Author
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Vigneswaran Y, Han H, De Loera R, Wen Y, Zhang X, Sun T, Mora-Solano C, and Collier JH
- Subjects
- Adjuvants, Immunologic pharmacology, Amino Acid Sequence, Animals, Antibody Formation drug effects, Cytokines metabolism, Freund's Adjuvant pharmacology, Mice, Inbred C57BL, Nanofibers chemistry, Ovalbumin immunology, Peptides chemistry, Phenotype, T-Lymphocytes drug effects, T-Lymphocytes immunology, Tissue Scaffolds chemistry, Adaptive Immunity drug effects, Awards and Prizes, Biocompatible Materials pharmacology, Internship and Residency, Peptides pharmacology, Wound Healing drug effects
- Abstract
Biomaterials used in the context of tissue engineering or wound repair are commonly designed to be "nonimmunogenic." However, previously it has been observed that self-assembled peptide nanofiber materials are noninflammatory despite their immunogenicity, suggesting that they may be appropriate for use in wound-healing contexts. To test this hypothesis, mice were immunized with epitope-containing peptide self-assemblies until they maintained high antibody titers against the material, then gels of the same peptide assemblies were applied within full-thickness dermal wounds. In three different murine dermal-wounding models with different baseline healing rates, even significantly immunogenic peptide assemblies did not delay healing. Conversely, adjuvanted peptide assemblies, while raising similar antibody titers to unadjuvanted assemblies, did delay wound healing. Analysis of the healing wounds indicated that compared to adjuvanted peptide assemblies, the unadjuvanted assemblies exhibited a progression of the dominant T-cell subset from CD4(+) to CD8(+) cells in the wound, and CD4(+) cell populations displayed a more Th2-slanted response. These findings illustrate an example of a significant antibiomaterial adaptive immune response that does not adversely affect wound healing despite ongoing antibody production. This material would thus be considered "immunologically compatible" in this specific context rather than "nonimmunogenic," a designation that is expected to apply to a range of other protein- and peptide-based biomaterials in wound-healing and tissue-engineering applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1853-1862, 2016., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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3. Key role of the epithelium in chronic upper airways diseases.
- Author
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Gohy S, Hupin C, Ladjemi MZ, Hox V, and Pilette C
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- Chronic Disease, Humans, Inflammation immunology, Inflammation pathology, Respiratory Mucosa pathology, Respiratory Tract Diseases pathology, Adaptive Immunity, Allergens immunology, Respiratory Mucosa immunology, Respiratory Tract Diseases immunology
- Abstract
The respiratory epithelium of the upper airways is a first-line defence against inhaled irritants, pathogens and allergens. It ensures a physical barrier provided by apical junctions and mucociliary clearance to avoid excessive activation of the immune system. The epithelium also forms a chemical and immunological barrier, extensively equipped to protect the airways against external aggressions before the adaptive immune system is required. Under normal circumstances, the epithelium is capable of recovering rapidly after damage. This manuscript reviews these main properties of the upper airway epithelium as well as its reported impairments in chronic inflammatory diseases. The knowledge on normal epithelial functions and their dysregulation in upper airway diseases should help to design new epithelial-targeted treatments., (© 2019 John Wiley & Sons Ltd.)
- Published
- 2020
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4. Functional interactions between innate lymphoid cells and adaptive immunity.
- Author
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Sonnenberg GF and Hepworth MR
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- Animals, Antigen Presentation, Cell Communication, Cytokines physiology, Humans, Inflammatory Bowel Diseases immunology, Neoplasms immunology, Adaptive Immunity, Immunity, Innate, Lymphocytes immunology
- Abstract
Innate lymphoid cells (ILCs) are enriched at barrier surfaces of the mammalian body where they rapidly respond to host, microbial or environmental stimuli to promote immunity or tissue homeostasis. Furthermore, ILCs are dysregulated in multiple human diseases. Over the past decade, substantial advances have been made in identifying the heterogeneity and functional diversity of ILCs, which have revealed striking similarities to T cell subsets. However, emerging evidence indicates that ILCs also have a complex role in directly influencing the adaptive immune response in the context of development, homeostasis, infection or inflammation. In turn, adaptive immunity reciprocally regulates ILCs, which indicates that these interactions are a crucial determinant of immune responses within tissues. Here, we summarize our current understanding of functional interactions between ILCs and the adaptive immune system, discuss limitations and future areas of investigation, and consider the potential for these interactions to be therapeutically harnessed to benefit human health.
- Published
- 2019
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5. Tick-borne encephalitis and golden agers: position paper of the International Scientific Working Group on Tick-borne encephalitis (ISW-TBE)
- Author
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Mats Haglund, Robert Steffen, Göran Günther, Aukse Mickiene, Franz Strle, Benjamin Briggs, Henrieta Hudečková, Michael Keller, Eva Jilkova, Zsuzsanna Jelenik, and Birger Sandell
- Subjects
Male ,Endemic Diseases ,Immunization, Secondary ,Severe disease ,Disease ,Adaptive Immunity ,Antibodies, Viral ,Leisure Activities ,Risk Factors ,medicine ,Immune Tolerance ,Humans ,Life Style ,Aged ,Aged, 80 and over ,Evidence-Based Medicine ,business.industry ,Tick-borne encephalitis ,Viral Vaccines ,General Medicine ,Middle Aged ,medicine.disease ,Vaccination ,Europe ,Immunization ,Immunology ,Primary immunization ,Position paper ,Female ,business ,Encephalitis ,Encephalitis, Tick-Borne ,Demography - Abstract
One of the primary goals of the 11th Annual Meeting of the International Scientific Working Group on Tick-borne encephalitis (ISW-TBE) held in 2009 was to develop the first update of the Position Paper on TBE in Golden Agers, summarizing the most essential aspects of the disease in this age group. TBE morbidity has continued to increase in recent years, which is thought to be due to an interplay of social, political, ecological, economic and demographic factors combined with climate changes. Today's golden agers i.e. individuals aged 50 years or above, are healthier and more mobile, lead more active lifestyles and spend more time travelling and performing outdoor leisure activities. This places them at an increased risk of infection. At the same time, increasing age is associated with a quantitative and qualitative decline in innate and adaptive immunity, which is why elderly individuals are more susceptible to infection and severe disease than younger people. Also, their response to vaccination tends to be slower, antibody titres generally reach lower levels and titres tend to decrease earlier than in younger individuals. Evidence is accumulating that this is also the case with TBE vaccination, emphasizing the importance of administering the first TBE booster vaccination no later than 3 years after the completion of primary immunization or at an even shorter interval. Encouragingly, recent data have shown that the field effectiveness of TBE vaccination exceeds 97%, with no significant differences between age groups.
- Published
- 2010
6. Cytotoxicity of zinc oxide nanoparticles to innate and adaptive human immune cells.
- Author
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Czyżowska A and Barbasz A
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- Adaptive Immunity radiation effects, Apoptosis drug effects, Caspases metabolism, Cell Line, Cell Membrane drug effects, Cell Membrane pathology, Humans, Immunity, Cellular radiation effects, Immunity, Innate radiation effects, Inflammation chemically induced, Lipid Peroxidation drug effects, Mitochondria drug effects, Oxidative Stress drug effects, Particle Size, Reactive Oxygen Species, Signal Transduction drug effects, Ultraviolet Rays, Adaptive Immunity drug effects, Immunity, Cellular drug effects, Immunity, Innate drug effects, Metal Nanoparticles toxicity, Zinc Oxide toxicity
- Abstract
Zinc oxide nanoparticles (ZnO-NPs) are widely used in almost every area of life. Therefore, exposure to them is unavoidable, which makes it necessary to assess their safety for humans. This paper aims to determine toxicity of ZnO-NPs of two diameters toward human immune cells responsible for: innate response (U-937 and HL-60) and acquired response (COLO-720L and HUT-78). Mitochondrial activity, membrane integrity, degree of cellular lipid oxidation, induction of inflammation, and activation of the apoptosis pathway were evaluated to determine differences in cellular response to the tested nanoparticles. ZnO-NPs with a diameter of 100 and 130 nm cause significant cell mortality at 25 and 12 mg/L, respectively. Mitochondrial damage leads to the activation of the caspase cascade and, consequently, to cell apoptosis. ZnO-NPs also cause peroxidation of membrane lipids. Due to the photocatalytic properties of ZnO-NPs, the effect of ultraviolet (UV) irradiation on the degree of their toxicity was also investigated. However, UV irradiation enhances the toxic effect of nanoparticles mainly by weakening the cell's defense capabilities. ZnO-NPs are cytotoxic to human immune system, and they may cause both long-term and short-term negative effects., (© 2020 John Wiley & Sons, Ltd.)
- Published
- 2021
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7. Sex-based trade-offs in the innate and acquired immune systems of Sternotherus minor.
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López-Pérez JE, Meylan PA, and Goessling JM
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- Animals, Blood Bactericidal Activity, Female, Hemagglutination Tests, Leukocyte Count, Longevity immunology, Male, Sex Factors, Testosterone blood, Adaptive Immunity immunology, Immunity, Innate immunology, Turtles immunology
- Abstract
Longevity patterns in most vertebrates suggest that females benefit most from maintenance investment. A reversed longevity pattern in loggerhead musk turtles (Sternotherus minor) allowed us to test trade-offs between maintenance and survivorship. We tested the hypothesis that the sex with greater longevity has greater maintenance than the sex with shorter longevity. We also compared the following parameters between sexes: Bactericidal ability (BA) and heterophil:lymphocyte ratios (HLR). Baseline blood samples were collected from turtles in the field; a subset of turtles was returned to a laboratory for experiments of acquired immune responses to sheep red blood cells (SRBC). We found no support for the original hypothesis of reversal in sex-dependent immune trade-offs (difference between sex SRBC titers: p = .102; interaction between treatment and sex: p = .177; difference between treatments: p < .001; effect of sex on BA: p = .830; effect of sex on HLR: p = .717). However, we did find support for sex-dependent differences in immunity in the relationship between HLR and body condition (BCI) (effect of BCI on HLR: p = .015). In field conditions, we found that males with higher body condition indices express stressed phenotypes more than males with lower body condition indices (p = .002). However, females expressed similar stress loads across all body conditions (p = .900). Testosterone concentrations were assayed in free-living turtles and were not related to any of the immune parameters. Our results suggest that the immune systems play an important role in balancing sex-specific responses to different selective pressures in S. minor., (© 2020 Wiley Periodicals LLC.)
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- 2020
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8. Interferon-λ orchestrates innate and adaptive mucosal immune responses.
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Ye L, Schnepf D, and Staeheli P
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- Animals, Humans, Infections immunology, Intestinal Mucosa immunology, Neutrophils immunology, Respiratory System immunology, Signal Transduction physiology, Adaptive Immunity, Immunity, Innate, Immunity, Mucosal, Interferon-gamma physiology
- Abstract
Type III interferon (IFN-λ) was initially thought to have functions similar to those of the type I interferons (IFN-α and IFN-β). New findings have indicated, however, that IFN-λ has a non-redundant role in the innate antiviral, antifungal and antiprotozoal defences of mucosal barriers. In this Review, we highlight recent work showing that IFN-λ inhibits virus dissemination within the body and limits the transmission of respiratory and gastrointestinal viruses to naive hosts. We also discuss findings indicating that IFN-λ can act on neutrophils to prevent invasive pulmonary aspergillosis. We summarize results showing that IFN-λ signalling differs in several respects from IFN-α and IFN-β signalling, particularly in neutrophils. Finally, we discuss new findings indicating that IFN-λ is a potent enhancer of adaptive immune responses in the respiratory mucosa.
- Published
- 2019
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9. Rubella vaccines: WHO position paper
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Contraindications ,Infant ,Adaptive Immunity ,World Health Organization ,Mass Vaccination ,Pregnancy ,Population Surveillance ,Humans ,Female ,Rubella Vaccine ,Pregnancy Complications, Infectious ,Child ,Epidemics ,Rubella virus ,Immunization Schedule ,Rubella - Published
- 2011
10. Just not himself these days: an invitation to submit papers on the topic of inflammation and immunity in organ systems physiology and pathophysiology
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David G. Harrison
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Inflammation ,Publishing ,Phrase ,Physiology ,Interpretation (philosophy) ,media_common.quotation_subject ,Immunity ,Autoimmunity ,Adaptive Immunity ,Immunity, Innate ,Reflexive pronoun ,Autoimmune Diseases ,Disease Models, Animal ,Physiology (medical) ,Distraction ,Personality ,Animals ,Humans ,Psychology ,Organ system ,media_common - Abstract
when someone is acting oddly, it is often said that she or he is “not herself” or “not himself.” This generally refers to a change is personality, either due to distraction, stress, or some other emotional alteration. During the past decade, a new interpretation of this phrase has arisen.
- Published
- 2011
11. Research progress on the immunological functions of Piezo1 a receptor molecule that responds to mechanical force.
- Author
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Xing H, Liu H, Chang Z, and Zhang J
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- Humans, Animals, Mechanotransduction, Cellular immunology, Calcium metabolism, Ion Channels metabolism, Adaptive Immunity, Immunity, Innate
- Abstract
The human immune system is capable of defending against, monitoring, and self-stabilizing various immune cells. Differentiation, proliferation, and development of these cells are regulated by biochemical signals. Moreover, biophysical signals, such as mechanical forces, have been found to affect immune cell function, thus introducing a new area of immunological research. Piezo1, a mechanically sensitive ion channel, was awarded the Nobel Prize for Physiology and Medicine in 2021. This channel is present on the surface of many cells, and when stimulated by mechanical force, it controls calcium (Ca
2+ ) inside the cells, leading to changes in downstream signals and thus regulating cell functions. Piezo1 is also expressed in various innate and adaptive immune cells and plays a major role in the immune function. In this review, we will explore the physiological functions and regulatory mechanisms of Piezo1 and its impact on innate and adaptive immunity. This may offer new insights into diagnostics and therapeutics for the prevention and treatment of diseases and surgical infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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12. Activating adaptive immunity by bispecific, T-cell engager antibodies bridging infected and immune-effector cells is a promising novel therapy for chronic hepatitis B.
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Xie Z and Protzer U
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- Humans, Antiviral Agents therapeutic use, Antiviral Agents pharmacology, Animals, Hepatitis B, Chronic immunology, Hepatitis B, Chronic drug therapy, Hepatitis B, Chronic therapy, Antibodies, Bispecific therapeutic use, Antibodies, Bispecific immunology, T-Lymphocytes immunology, Adaptive Immunity, Hepatitis B virus immunology, Immunotherapy methods
- Abstract
Bispecific antibodies (bsAbs) are engineered immunoglobulins that combine two different antigen-binding sites in one molecule. BsAbs can be divided into two molecular formats: IgG-like and non-IgG-like antibodies. Structural elements of each format have implications for engaging the immune system. T cell engager antibodies (TCEs) are bsAbs designed to engage T cells with target cells. TCEs can be applied not only in cancer but also in infectious disease therapy to activate T-cell responses. In this review, we focus on current literature on the design and use of bsAbs as an innovative strategy to enhance adaptive antiviral immune responses. We summarized the novel T cell-related immunotherapies with a focus on TCEs, that are developed for the treatment of chronic hepatitis B. Chronic infection with the hepatitis B virus (HBV) had a death toll of 1.1 million humans in 2022, mainly due to liver cirrhosis and hepatocellular carcinoma developing in the more than 250 million humans chronically infected. A curative treatment approach for chronic hepatitis B is lacking. Combining antiviral therapy with immune therapies activating T-cell responses is regarded as the most promising therapeutic approach to curing HBV and preventing the sequelae of chronic infection. Attracting functionally intact T cells that are not HBV-specific and, therefore, have not yet been exposed to regulatory mechanisms and activating those at the target site in the liver is a very interesting therapeutic approach that could be achieved by TCEs. Thus, TCEs redirecting T cells toward HBV-positive cells represent a promising strategy for treating chronic hepatitis B and HBV-associated hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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13. Modulatory effects of gut microbiota on innate and adaptive immune responses following spinal cord injury.
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Zhu L, Wang F, Xing J, Hu X, Gou X, Li J, Pang R, and Zhang A
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- Humans, Animals, Brain-Gut Axis physiology, Dysbiosis immunology, Spinal Cord Injuries immunology, Spinal Cord Injuries microbiology, Gastrointestinal Microbiome immunology, Gastrointestinal Microbiome physiology, Immunity, Innate, Adaptive Immunity immunology
- Abstract
Spinal cord injury (SCI) represents a highly debilitating trauma to the central nervous system, currently lacking effective therapeutic strategies. The cascade of inflammatory responses induced by secondary damage following SCI disrupts the local immune environment at the injury site, ultimately exacerbating functional impairments post-injury. With advancing research on the gut-brain axis, evidence suggests that dysbiosis of the gut microbiota post-SCI amplifies inflammatory responses and plays a pivotal role in modulating post-injury immune-inflammatory responses. In this review article, we will explore the significant role of the gut microbiota and its metabolic products in modulating the responses of central and peripheral immune cells post-SCI, as well as their potential as therapeutic interventions for SCI treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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14. Type 17 immune response promotes oral epithelial cell proliferation in periodontitis.
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Zhou Y, Lv D, Wei W, Zhou T, Tang S, Yang F, Zhang J, Jiang L, Xia X, Jiang Y, Chen Q, Yue Y, and Feng X
- Subjects
- Animals, Mice, Disease Models, Animal, Protein Transport immunology, Keratinocytes cytology, Keratinocytes immunology, Humans, Cell Line, Alveolar Bone Loss immunology, Periodontitis immunology, Epithelial Cells cytology, Epithelial Cells immunology, Cell Proliferation genetics, Interleukin-17 genetics, Interleukin-17 immunology, Adaptive Immunity immunology
- Abstract
Objectives: This study aims to investigate the effects of type 17 immune response on the proliferation of oral epithelial cells in periodontitis., Design: A time-dependent ligature induced periodontitis mouse model was utilized to explore gingival hyperplasia and the infiltration of interleukin 17A (IL-17A) positive cells. Immunohistochemistry and flow cytometry were employed to determine the localization and expression of IL-17A in the ligature induced periodontitis model. A pre-existing single-cell RNA sequencing dataset, comparing individuals affected by periodontitis with healthy counterparts, was reanalyzed to evaluate IL-17A expression levels. We examined proliferation markers, including proliferating cell nuclear antigen (PCNA), signal transducer and activator of transcription (STAT3), Yes-associated protein (YAP), and c-JUN, in the gingival and tongue epithelium of the periodontitis model. An anti-IL-17A agent was administered daily to observe proliferative changes in the oral mucosa within the periodontitis model. Cell number quantification, immunofluorescence, and western blot analyses were performed to assess the proliferative responses of human normal oral keratinocytes to IL-17A treatment in vitro., Results: The ligature induced periodontitis model exhibited a marked infiltration of IL-17A-positive cells, alongside significant increase in thickness of the gingival and tongue epithelium. IL-17A triggers the proliferation of human normal oral keratinocytes, accompanied by upregulation of PCNA, STAT3, YAP, and c-JUN. The administration of an anti-IL-17A agent attenuated the proliferation in oral mucosa., Conclusions: These findings indicate that type 17 immune response, in response to periodontitis, facilitates the proliferation of oral epithelial cells, thus highlighting its crucial role in maintaining the oral epithelial barrier., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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15. Bergenin potentiates BCG efficacy by enriching mycobacteria-specific adaptive memory responses via the Akt-Foxo-Stat4 axis.
- Author
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Mukhopadhyay S, Pahuja I, Okieh AA, Pandey D, Yadav V, Bhaskar A, and Dwivedi VP
- Subjects
- Animals, Female, Tuberculosis immunology, Tuberculosis microbiology, Host-Pathogen Interactions, Disease Models, Animal, Forkhead Transcription Factors metabolism, Mice, BCG Vaccine immunology, BCG Vaccine pharmacology, Immunologic Memory drug effects, Proto-Oncogene Proteins c-akt metabolism, Mycobacterium tuberculosis immunology, Mice, Inbred C57BL, Benzopyrans pharmacology, Signal Transduction, STAT4 Transcription Factor metabolism, Adaptive Immunity drug effects
- Abstract
The extensive inability of the BCG vaccine to produce long-term immune protection has not only accelerated the disease burden but also progressed towards the onset of drug resistance. In our previous study, we have reported the promising effects of Bergenin (Berg) in imparting significant protection as an adjunct immunomodulator against tuberculosis (TB). In congruence with our investigations, we delineated the impact of Berg on T cells, wherein it enhanced adaptive memory responses by modulating key transcription factors, STAT4 and Akt. We translated this finding into the vaccine model of TB and observed a notable reduction in the burden of Mycobacterium tuberculosis (M.tb) in BCG-Berg co-immunized mice as compared to BCG vaccination. Moreover, Berg, along with BCG, also aided in a heightened proinflammatory response milieu that corroborates the host protective immune response against TB. Furthermore, this response aligns with the escalated central and resident memory responses by modulating the Akt-Foxo-Stat4 axis, which plays a crucial role in enhancing the vaccine efficacy of BCG. These findings showcase the utilization of immunomodulator Berg as an immunoprophylactic agent to upgrade immunological memory, making it a more effective defender against TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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16. Differences in the dynamics of the <scp>tandem‐SH2</scp> modules of the Syk and <scp>ZAP</scp> ‐70 tyrosine kinases
- Author
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Neel H. Shah, Christine L. Gee, John Kuriyan, Jean M. Badroos, Helen T. Hobbs, and Susan Marqusee
- Subjects
Protein Conformation, alpha-Helical ,Conformational change ,Full‐Length Papers ,T-Lymphocytes ,Genetic Vectors ,Gene Expression ,Syk ,chemical and pharmacologic phenomena ,Adaptive Immunity ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,SH2 domain ,Biochemistry ,Full‐Length Paper ,evolution ,Immunoreceptor tyrosine-based activation motif ,Escherichia coli ,Animals ,Humans ,Syk Kinase ,Protein Interaction Domains and Motifs ,Cloning, Molecular ,Tyrosine ,Molecular Biology ,B-Lymphocytes ,Binding Sites ,ZAP-70 Protein-Tyrosine Kinase ,Chemistry ,conformational landscape ,hydrogen–deuterium exchange mass spectrometry ,tyrosine kinase signaling ,Deuterium Exchange Measurement ,hemic and immune systems ,Biological Evolution ,Recombinant Proteins ,Protein kinase domain ,protein dynamics ,Biophysics ,Phosphorylation ,Protein Conformation, beta-Strand ,Tyrosine kinase ,Protein Binding ,Signal Transduction - Abstract
The catalytic activity of Syk‐family tyrosine kinases is regulated by a tandem Src homology 2 module (tSH2 module). In the autoinhibited state, this module adopts a conformation that stabilizes an inactive conformation of the kinase domain. The binding of the tSH2 module to phosphorylated immunoreceptor tyrosine‐based activation motifs necessitates a conformational change, thereby relieving kinase inhibition and promoting activation. We determined the crystal structure of the isolated tSH2 module of Syk and find, in contrast to ZAP‐70, that its conformation more closely resembles that of the peptide‐bound state, rather than the autoinhibited state. Hydrogen–deuterium exchange by mass spectrometry, as well as molecular dynamics simulations, reveal that the dynamics of the tSH2 modules of Syk and ZAP‐70 differ, with most of these differences occurring in the C‐terminal SH2 domain. Our data suggest that the conformational landscapes of the tSH2 modules in Syk and ZAP‐70 have been tuned differently, such that the autoinhibited conformation of the Syk tSH2 module is less stable. This feature of Syk likely contributes to its ability to more readily escape autoinhibition when compared to ZAP‐70, consistent with tighter control of downstream signaling pathways in T cells., PDB Code(s): 7SA7
- Published
- 2021
17. Cascade catalysis nanozyme for interfacial functionalization in combating implant infections associated with diabetes via sonodynamic therapy and adaptive immune activation.
- Author
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Xu K, Zou Y, Lin C, Zhang L, Tan M, Li M, Wu J, Li X, He Y, Liu P, Li K, and Cai K
- Subjects
- Animals, Catalysis, Mice, Dendritic Cells immunology, Reactive Oxygen Species metabolism, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents chemistry, Prostheses and Implants, Hydrogen Peroxide, Diabetes Mellitus, Experimental therapy, Mice, Inbred C57BL, Adaptive Immunity drug effects, Ultrasonic Therapy methods, Titanium chemistry, Manganese Compounds chemistry, Manganese Compounds pharmacology, Oxides chemistry
- Abstract
Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO
2 NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H2 O2 ) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn2+ facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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18. Major vault protein directly enhances adaptive immunity induced by Influenza A virus or indirectly through innate immunity.
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Ma C, Luo C, Deng F, Yu C, Chen Y, Zhong G, Zhan Y, Nie L, Huang Y, Xia Y, Cai Z, Xu K, Cai H, Wang F, Lu Z, Zeng X, Zhu Y, and Liu S
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Germinal Center immunology, B-Lymphocytes immunology, Immunity, Innate, Influenza A virus immunology, Vault Ribonucleoprotein Particles genetics, Vault Ribonucleoprotein Particles immunology, Vault Ribonucleoprotein Particles metabolism, Adaptive Immunity, Mice, Knockout, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, Dendritic Cells immunology
- Abstract
As we previously revealed, major vault protein (MVP) is a virus-induced host factor, and its expression is crucial for innate immune responses. Nevertheless, the function of MVP in adaptive immunity is poorly known. Here, we demonstrate that Mvp knockout mice had attenuated antibody responses and reduced survival after rechallenge with homologous influenza A virus (IAV) relative to wild-type mice. Analysis of B cell populations showed that MVP promoted germinal center (GC) responses to develop optimal antiviral humoral immunity. Although MVP-deficient T cells and dendritic cells (DCs) were not intrinsically damaged, MVP promoted activating effector T cells and T follicular helper responses and regulated specific DC subsets. These findings suggest that MVP directs an effective adaptive immune response against IAV by directly engaging in GC reactions or indirectly augmenting cellular immunity via innate immune pathways., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shi Liu reports financial support was provided by National Key Research and Development Program of China. Shi Liu reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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19. mRNA vaccines contribute to innate and adaptive immunity to enhance immune response in vivo.
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Cao Q, Fang H, and Tian H
- Subjects
- Humans, Animals, SARS-CoV-2 immunology, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Messenger immunology, Immunity, Innate, Adaptive Immunity, mRNA Vaccines, COVID-19 prevention & control, COVID-19 immunology, COVID-19 Vaccines immunology
- Abstract
Messenger RNA (mRNA) therapeutics have been widely employed as strategies for the treatment and prevention of diseases. Amid the global outbreak of COVID-19, mRNA vaccines have witnessed rapid development. Generally, in the case of mRNA vaccines, the initiation of the innate immune system serves as a prerequisite for triggering subsequent adaptive immune responses. Critical cells, cytokines, and chemokines within the innate immune system play crucial and beneficial roles in coordinating tailored immune reactions towards mRNA vaccines. Furthermore, immunostimulators and delivery systems play a significant role in augmenting the immune potency of mRNA vaccines. In this comprehensive review, we systematically delineate the latest advancements in mRNA vaccine research, present an in-depth exploration of strategies aimed at amplifying the immune effectiveness of mRNA vaccines, and offer some perspectives and recommendations regarding the future advancements in mRNA vaccine development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
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20. The importance of Ca 2+ microdomains for the adaptive immune response.
- Author
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Diercks BP
- Subjects
- Humans, Animals, Lymphocyte Activation immunology, Membrane Microdomains metabolism, Membrane Microdomains immunology, Adaptive Immunity, Calcium Signaling, T-Lymphocytes immunology, T-Lymphocytes metabolism, Calcium metabolism, Receptors, Antigen, T-Cell metabolism, Receptors, Antigen, T-Cell immunology
- Abstract
Calcium signaling stands out as the most widespread and universally used signaling system and is of utmost importance for immunity. Controlled elevations in cytosolic and organellar Ca
2+ concentrations in T cells control complex and essential effector functions including proliferation, differentiation, cytokine secretion, and cytotoxicity, among others. Additionally, disruptions in Ca2+ regulation in T cells contribute to diverse autoimmune, inflammatory, and immunodeficiency conditions. Among the initial intracellular signals, which occurring even before T cell receptor (TCR) stimulation are highly localized, spatially and temporally restricted so-called Ca2+ microdomains, caused by adhesion to extracellular matrix proteins (ECM proteins). The Ca2+ microdomains present both before and within the initial seconds following TCR stimulation are likely to play a crucial role in fine-tuning the downstream activity of T cell activation and thus, shaping an adaptive immune response. In this review, the emphasis is on the recent advances of adhesion-dependent Ca2+ microdomains (ADCM) in the absence of TCR stimulation, initial Ca2+ microdomains evoked by TCR stimulation (TDCM), the downstream signaling processes as well as possible therapeutic targets for interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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21. Development of innate and adaptive immunity to RSV in young children.
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Parsons EL, Kim JS, and Malloy AMW
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- Humans, Infant, Respiratory Syncytial Virus Vaccines immunology, Respiratory Syncytial Virus, Human immunology, Child, Preschool, Antibodies, Viral immunology, Female, Respiratory Syncytial Viruses immunology, Respiratory Syncytial Virus Infections immunology, Respiratory Syncytial Virus Infections prevention & control, Adaptive Immunity immunology, Immunity, Innate immunology
- Abstract
Infection of the respiratory tract with respiratory syncytial virus (RSV) is common and occurs repeatedly throughout life with most severe disease occurring at the extremes of age: in young infants and the elderly. Effective anti-viral therapeutics are not available and therefore prevention has been the primary strategy for reducing the disease burden. Our current understanding of respiratory mucosal cell biology and the immune response within the respiratory tract is inadequate to prevent infection caused by a pathogen like RSV that does not disseminate outside of this environment. Gaps in our understanding of the activation of innate and adaptive immunity in response to RSV and the role of age upon infection also limit improvements in the design of therapeutics and vaccines for young infants. However, advancements in structural biology have improved our ability to characterize antibodies against viral proteins and in 2023 the first vaccines for those over 60 years and pregnant women became available, potentially reducing the burden of disease. This review will examine our current understanding of the critical facets of anti-RSV immune responses in infants and young children as well as highlight areas where more research is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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22. Immune consequences of exercise in hypoxia: A narrative review.
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Burtscher J, Pasha Q, Chanana N, Millet GP, Burtscher M, and Strasser B
- Subjects
- Humans, Immunity, Innate physiology, Altitude, Oxygen metabolism, Acclimatization physiology, Immune System physiology, Adaptation, Physiological, Exercise physiology, Hypoxia immunology, Adaptive Immunity
- Abstract
Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type, dose (frequency/duration, intensity), and individual characteristics. Similarly, reduced availability of ambient oxygen (hypoxia) modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia. How combined exercise and hypoxia (e.g., high-altitude training) sculpts immune responses is not well understood, although such combinations are becoming increasingly popular. Therefore, in this paper, we summarize the impact on immune responses of exercise and of hypoxia, both independently and together, with a focus on specialized cells in the innate and adaptive immune system. We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia, then we discuss how they may be modulated by nutritional strategies. Mitochondrial, antioxidant, and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism, resilience, and overall immune functions by regulating the survival, differentiation, activation, and migration of immune cells. This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions. Appropriate acclimatization, training, and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state., (Copyright © 2023. Production and hosting by Elsevier B.V.)
- Published
- 2024
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23. Dynamical analysis of a general delayed HBV infection model with capsids and adaptive immune response in presence of exposed infected hepatocytes.
- Author
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Foko S
- Subjects
- Humans, Models, Immunological, T-Lymphocytes, Cytotoxic immunology, Basic Reproduction Number statistics & numerical data, B-Lymphocytes immunology, DNA, Viral immunology, Models, Biological, Hepatocytes immunology, Hepatocytes virology, Hepatitis B virus immunology, Capsid immunology, Adaptive Immunity immunology, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology, Hepatitis B, Chronic transmission, Computer Simulation, Mathematical Concepts
- Abstract
The aim of this paper is to develop and investigate a novel mathematical model of the dynamical behaviors of chronic hepatitis B virus infection. The model includes exposed infected hepatocytes, intracellular HBV DNA-containing capsids, uses a general incidence function for viral infection covering a variety of special cases available in the literature, and describes the interaction of cytotoxic T lymphocytes that kill the infected hepatocytes and the magnitude of B-cells that send antibody immune defense to neutralize free virions. Further, one time delay is incorporated to account for actual capsids production. The other time delays are used to account for maturation of capsids and free viruses. We start with the analysis of the proposed model by establishing the local and global existence, uniqueness, non-negativity and boundedness of solutions. After defined the threshold parameters, we discuss the stability properties of all possible steady state constants by using the crafty Lyapunov functionals, the LaSalle's invariance principle and linearization methods. The impacts of the three time delays on the HBV infection transmission are discussed through local and global sensitivity analysis of the basic reproduction number and of the classes of infected states. Finally, an application is provided and numerical simulations are performed to illustrate and interpret the theoretical results obtained. It is suggested that, a good strategy to eradicate or to control HBV infection within a host should concentrate on any drugs that may prolong the values of the three delays., (© 2024. The Author(s).)
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- 2024
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24. Type III interferons in innate and adaptive immunity in the respiratory tract.
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Piperakis A, Galani IE, and Andreakos E
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- Humans, Animals, Signal Transduction immunology, Interferon Type I metabolism, Interferon Type I immunology, Immunity, Innate, Adaptive Immunity, Interferons metabolism, Interferons immunology, Respiratory System immunology, Respiratory System metabolism, Interferon Lambda
- Abstract
Lambda interferons (IFNλs), also termed type III interferons (IFNs) or interleukins-28/29, have been in the shadow of type I IFNs for a long time. Their common induction mechanisms and signalling cascades with type I IFNs have made difficult the unwinding of their unique nonredundant functions. However, this is now changing with mounting evidence supporting a major role of IFNλs as a specialized antiviral defense system in the body, mediating protection at mucosal barrier surfaces while limiting immunopathology. Here, we review the latest progress on the complex activities of IFNλs in the respiratory tract, focusing on their multiple effects in IFNλ receptor-expressing cells, the modulation of innate and adaptive immune responses in the context of infections and respiratory diseases, and their similarities and differences with type I IFNs. We also discuss their potential in therapeutic applications and the most recent developments in that direction., Competing Interests: Declaration of Competing Interest E.A. is an inventor in a patent on interferon lambda. The remaining authors declare no competing financial interests.The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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25. The methods and advances of adaptive immune receptors repertoire sequencing
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Akihiko Yoshimura, Nongyue He, Wenjing Pan, Yujie Tang, Song Li, Hongmei Liu, Haijing Wu, Congli Tang, and Yan Deng
- Subjects
Computer science ,T-Lymphocytes ,Population ,adaptive immune repertoire sequencing ,Medicine (miscellaneous) ,Computational biology ,Adaptive Immunity ,DNA sequencing ,Immune system ,Antigen ,Humans ,Receptors, Immunologic ,education ,Receptor ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,education.field_of_study ,B-Lymphocytes ,Repertoire ,high-throughput sequencing ,Computational Biology ,High-Throughput Nucleotide Sequencing ,bioinformatics ,Acquired immune system ,T or B cell receptors ,Experimental methods ,Single-Cell Analysis ,Research Paper - Abstract
The adaptive immune response is a powerful tool, capable of recognizing, binding to, and neutralizing a vast number of internal and external threats via T or B lymphatic receptors with widespread sets of antigen specificities. The emergence of high-throughput sequencing technology and bioinformatics provides opportunities for research in the fields of life sciences and medicine. The analysis and annotation for immune repertoire data can reveal biologically meaningful information, including immune prediction, target antigens, and effective evaluation. Continuous improvements of the immunological repertoire sequencing methods and analysis tools will help to minimize the experimental and calculation errors and realize the immunological information to meet the clinical requirements. That said, the clinical application of adaptive immune repertoire sequencing requires appropriate experimental methods and standard analytical tools. At the population cell level, we can acquire the overview of cell groups, but the information about a single cell is not obtained accurately. The information that is ignored may be crucial for understanding the heterogeneity of each cell, gene expression and drug response. The combination of high-throughput sequencing and single-cell technology allows us to obtain single-cell information with low-cost and high-throughput. In this review, we summarized the current methods and progress in this area.
- Published
- 2021
26. Altered expression of genes related to innate antifungal immunity in the absence of galectin-3
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André Moreira Pessoni, Patrícia Kellen Martins Oliveira Brito, Gustavo H. Goldman, Caroline Patini Rezende, Thiago Aparecido da Silva, and Fausto Almeida
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Microbiology (medical) ,Antifungal ,Antifungal Agents ,animal structures ,medicine.drug_class ,Galectin 3 ,Galectins ,Immunology ,Infectious and parasitic diseases ,RC109-216 ,Adaptive Immunity ,Biology ,Microbiology ,gene knockout ,Mice ,03 medical and health sciences ,Immunity ,galectin-3 ,Gene expression ,otorhinolaryngologic diseases ,medicine ,Animals ,Gene ,Gene knockout ,030304 developmental biology ,Galectin ,0303 health sciences ,Innate immune system ,030306 microbiology ,EXPRESSÃO GÊNICA ,Immunity, Innate ,Cell biology ,stomatognathic diseases ,Infectious Diseases ,Galectin-3 ,innate immune response ,gene expression ,Parasitology ,antifungal immunity ,Research Article ,Research Paper - Abstract
Galectin-3 (Gal-3) is the most studied member of the animal galectin family, which comprises β-galactoside-binding lectins and participates in several cellular events. Its expression in cells involved in innate and adaptive immunity is related to anti- and proinflammatory functions, signaling an important role in inflammatory, infectious, and tumorigenesis processes. Mice deficient in Gal-3 exhibit important phenotypes, but it is unclear whether these phenotypes reflect an impairment of the functions of this protein. Gal-3 plays an important role in modulating the immune response to different pathogenic microorganisms. However, the role of Gal-3 in immunity to infection is still poorly understood. Therefore, we investigated the effects of Gal-3 deletion on the expression of genes involved in the innate immune response in the lungs, spleens, and brains of Gal-3 KO mice. Gene profiling expression analysis suggested that Gal-3 deletion resulted in differentially modulated expression of the genes encoding beta-glucan, mannose and chitin-responsive pattern recognition receptors, signal transduction, inflammation, and phagocytosis. Our data thus suggest the importance of Gal-3 expression in the host innate immune system.
- Published
- 2021
27. A spontaneous multifunctional hydrogel vaccine amplifies the innate immune response to launch a powerful antitumor adaptive immune response
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Shunyao Zhu, Miaomiao Zhang, Songlin Gong, Changyang Gong, Tao He, Qinjie Wu, Xinchao Li, Xiuqi Liang, and Lu Li
- Subjects
Ovalbumin ,T-Lymphocytes ,medicine.medical_treatment ,Medicine (miscellaneous) ,chemical and pharmacologic phenomena ,02 engineering and technology ,Adaptive Immunity ,Biology ,Cancer Vaccines ,Mannans ,Mice ,03 medical and health sciences ,Immune system ,Cancer immunotherapy ,Antigen ,Cell Line, Tumor ,Tumor Microenvironment ,medicine ,Animals ,Melanoma ,innate immunity ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Schiff Bases ,030304 developmental biology ,Inflammation ,Chitosan ,0303 health sciences ,Ncom Gel vaccine ,cancer immunotherapy ,Innate immune system ,Macrophages ,Hydrogels ,Dendritic Cells ,Immunotherapy ,021001 nanoscience & nanotechnology ,Acquired immune system ,Immunity, Innate ,adaptive immune response ,Tumor antigen ,Mice, Inbred C57BL ,spontaneous multifunctional hydrogel ,Humoral immunity ,Microscopy, Electron, Scanning ,Cancer research ,Female ,Rheology ,0210 nano-technology ,Research Paper - Abstract
Substantial progress has been made with cancer immunotherapeutic strategies in recent years, most of which mainly rely on enhancing the T cell response. However, sufficient tumor antigen information often cannot be presented to T cells, resulting in a failed effector T cell response. The innate immune system can effectively recognize tumor antigens and then initiate an adaptive immune response. Here, we developed a spontaneous multifunctional hydrogel (NOCC-CpG/OX-M, Ncom Gel) vaccine to amplify the innate immune response and harness innate immunity to launch and maintain a powerful adaptive immune response. Methods: Ncom Gel was formed by a Schiff base reaction between CpG-modified carboxymethyl chitosan (NOCC-CpG) and partially oxidized mannan (OX-M). The effects of the Ncom Gel vaccine on DCs and macrophages in vitro and antigen-specific humoral immunity and cellular immunity in vivo were studied. Furthermore, the antitumor immune response of the Ncom Gel vaccine and its effect on the tumor microenvironment were evaluated. Results: The Ncom Gel vaccine enhanced antigen presentation to T cells by facilitating DC uptake and maturation and inducing macrophages to a proinflammatory subtype, further leading to a T cell-mediated adaptive immune response. Moreover, the innate immune response could be amplified via the promotion of antigen-specific antibody production. The Ncom Gel vaccine reversed the tumor immune microenvironment to an inflamed phenotype and showed a significant antitumor response in a melanoma model. Conclusions: Our research implies the potential application of injectable hydrogels as a platform for tumor immunotherapy. The strategy also opens up a new avenue for multilayered cancer immunotherapy.
- Published
- 2021
28. The effect of repetitive exposure to intravenous anesthetic agents on the immunity in mice
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Liyun Piao, Seong-Hyop Kim, Eun-Hye Seo, Hyun-Jun Park, and Seung Hyun Lee
- Subjects
CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Midazolam ,medicine.medical_treatment ,Enzyme-Linked Immunosorbent Assay ,Adaptive Immunity ,Pharmacology ,Kidney ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Dexmedetomidine ,Mice, Inbred BALB C ,propofol ,Cluster of differentiation ,business.industry ,dexmedetomidine ,General Medicine ,Immunohistochemistry ,immunity ,Cytokine ,medicine.anatomical_structure ,Liver ,Anesthetic ,intravenous anesthetic agent ,030211 gastroenterology & hepatology ,Histopathology ,Propofol ,business ,Anesthetics, Intravenous ,Research Paper ,medicine.drug - Abstract
Introduction: This study was designed to assess the effect of repetitive exposure to intravenous anesthetic agents on the immunity in mice. Materials and Methods: The mice were divided into six groups: three intravenous anesthetic agents groups (dexmedetomidine, midazolam and propofol groups), and three corresponding control groups (CD, CM, and CP groups). The intravenous injections were administered once per day for 5 days. The immunity of mice was checked after the last intravenous injection. Histopathology and immunochemistry of liver and kidneys were evaluated. Cytokine levels in the blood was also checked. vs. evaluated with cytokine levels in the blood. Results: Cluster of differentiation (CD)4+ T cells were significantly less expressed in dexmedetomidine and propofol groups, compared with the corresponding control groups [34.08 ± 5.63% in the dexmedetomidine group vs. 59.74 ± 8.64% in the CD group, p < 0.05; 25.28 ± 7.28% in the propofol group vs. 61.12 ± 2.70% in the Cp group, p < 0.05]. Apoptosis of CD4+ T cells was increased significantly in dexmedetomidine and propofol groups, compared with the corresponding control groups. Histopathological findings of liver and kidneys did not show any specific differences of any of three intravenous anesthetic agents groups with their corresponding control groups, although immunohistochemical examination indicated significantly lower expression of Toll-like receptor-4 from liver and kidneys in dexmedetomidine and propofol groups. The cytokine levels were not different between the groups. Conclusion: Repetitive exposure to dexmedetomidine and propofol reduced the expression of CD4+ T cells but did not induce any significant liver or kidney injuries.
- Published
- 2020
29. Novel calreticulin-nanoparticle in combination with focused ultrasound induces immunogenic cell death in melanoma to enhance antitumor immunity
- Author
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Mohit Pratap Singh, P. Jack Hoopes, Jerry R. Malayer, Shitao Li, Sri Nandhini Sethuraman, Steven Fiering, Ashish Ranjan, Girish Patil, and Chandan Guha
- Subjects
0301 basic medicine ,Ultrasonic Therapy ,Population ,Melanoma, Experimental ,Clone (cell biology) ,Medicine (miscellaneous) ,CD47 Antigen ,Immunogenic Cell Death ,Adaptive Immunity ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,calreticulin ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Tumor-Associated Macrophages ,melanoma ,Animals ,Humans ,Medicine ,education ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,education.field_of_study ,biology ,business.industry ,nanoparticle ,Melanoma ,Cell Membrane ,medicine.disease ,Combined Modality Therapy ,Xenograft Model Antitumor Assays ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,focused ultrasound ,Cytokines ,Nanoparticles ,Immunogenic cell death ,Lymph Nodes ,business ,Calreticulin ,Spleen ,CD8 ,Research Paper - Abstract
Rationale: Some studies have shown that the local activation of immunogenic cell death (ICD) by upregulating calreticulin (CRT) expression in solid tumors can improve antitumor effects. Although a promising approach, a key current challenge in ICD tumor therapy is the absence of a clinically translatable method for reproducibly inducing the CRT expression. Herein, we report a novel calreticulin-nanoparticle (CRT-NP) that enhances ICD and synergizes with focused ultrasound (FUS) to achieve local and systemic antitumor effects. Methods: Full-length clone DNA of calreticulin was encapsulated in NPs made from DOTAP and cholesterol. Three CRT-NP intratumoral injections of 20 µg each were given 2 days apart, and FUS heating (42-45°C, ~15min) was applied sequentially 24h after each injection to induce ICD. To investigate ICD specific immune effect, the splenocytes of mice vaccinated with CRT-NP (± FUS) treated B16F10 cells were evaluated ex-vivo for TRP-2 antigen specific immunity. Additionally, the long-term protection was evaluated by re-challenging with the melanoma cells in the flank regions of tumor bearing mice. Results: CRT-NP plus FUS (CFUS) upregulated CRT expression, expanded the population of melanoma TRP-2 specific functional CD4+ and CD8+ T cells and tumor-suppressing M1 phenotype, and increased PD-1 and PD-L1 marker expression in the T cells. Therapeutically, CFUS suppressed B16 melanoma growth by >85% vs. that seen in untreated controls, and >~50% vs. CRT-NP or FUS alone, and prevented tumor growth in distal untreated sites. Conclusions: CRT-NP amplifies the FUS and ICD therapeutic outcomes against melanoma, suggesting that the proposed combinatorial methodology may be clinically translatable.
- Published
- 2020
30. Immune signature and phagocytosis of circulating DC subsets in healthy adults during aging.
- Author
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Cui Q, Li W, Wang D, Wang S, Liu A, Zhang G, Yang Y, Ge T, He G, and Yu J
- Subjects
- Adult, Humans, Phenotype, Flow Cytometry methods, Aging, Dendritic Cells, Phagocytosis, Adaptive Immunity
- Abstract
Dendritic cells (DC) play a pivotal role in the onset and progression of immunosenescence-associated diseases, serving as a link between innate and adaptive immunity. Thus, there is a need to establish reference ranges for DC subset levels in healthy adults and investigate the potential impact of age on DC subset levels and phagocytic activity. Single-platform multi-color flow cytometry was performed to assess the proportions of circulating conventional type 1 DC (cDC1), conventional type 2 DC (cDC2), and plasmacytoid DC (pDC), as well as the percentages of CD80, CD86, CD83, PD-L1, and CD32 in cDC1, cDC2, and pDC. Reference ranges were established based on age and gender, and the percentage of circulating DC subsets in different age groups was compared. In addition, circulating DC were enriched using a magnetic bead sorting kit and co-cultured with polystyrene (PS) beads, categorized by age groups, followed by the evaluation of PS bead phagocytosis using light microscopy and flow cytometry. The results indicated that the percentages of circulating cDC1, cDC2, and CD32
+ cDC2 decreased with age (P < 0.05) and revealed age-related impairment in phagocytic percentage of cDC2 (P < 0.05). These findings provide a deeper understanding of the impact of age on the phenotype and phagocytic activity of DC subsets, shedding light on their role and function in immunosenescence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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31. The application of MARCO for immune regulation and treatment.
- Author
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Zhou G, Zhang L, and Shao S
- Subjects
- B-Lymphocytes, Macrophages, Phagocytosis, Immunotherapy, Adaptive Immunity
- Abstract
Macrophage receptor with collagen structure (MARCO) is a member of scavenger receptor class A (SR-A) and shares structural and functional similarities with SR-A1. In recent years, many studies have shown that MARCO can trigger an immune response and has therapeutic potential as a target for immunotherapy. Studies have shown that alterations in MARCO expression following pathogen infection cause changes in the functions of innate and adaptive immune cells, including macrophages, dendritic cells, B cells, and T cells, affecting the body's immune response to invading pathogens; thus, MARCO plays a crucial role in triggering the immune response, bridging innate and adaptive immunity, and eliminating pathogens. This paper is a comprehensive summary of the recent research on MARCO. This review focuses on the multiple functions of MARCO, including adhesion, migration, phagocytosis, and cytokine secretion with special emphasis on the complex interactions between MARCO and various types of cells involved in the immune response, as well as possible immune-related mechanisms. In summary, in this review, we discuss the structure and function of MARCO and its role in the immune response and highlight the therapeutic potential of MARCO as a target for immunotherapy. We hope that this review provides a theoretical basis for future research on MARCO., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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32. Editorial overview: Getting the house in order: Cell-intrinsic mechanisms of innate immune defence.
- Author
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Hartland EL and Shin S
- Subjects
- Humans, Immunity, Innate, Adaptive Immunity
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2024
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33. Adaptive post-COVID-19 immune response in female subjects of the Russian arctic region.
- Author
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Shchegoleva LS, Kabbani MS, Shashkova EY, Filippova OE, Popovskaya EV, Sergeeva TB, and Morozova OS
- Subjects
- Humans, Female, Russia epidemiology, Arctic Regions epidemiology, Adult, Young Adult, COVID-19 immunology, SARS-CoV-2 immunology, Adaptive Immunity immunology
- Abstract
The Arctic region's unfavorable living conditions adversely affect the spread of infectious diseases, including COVID-19, This, in turn, can also lead to increased morbidity and mortality rates in the area due to a number of factors such as climate, environment, and high prevalence rate of pre-existing health issues like diabetes, obesity, and respiratory infections. These circumstances adversely affect maintaining the level of working capability. The aim of this paper is to investigate the ratio of immunocompetent cells involved in the adaptive post-COVID-19 immune response. The research includes an immunological assessment of 29 women aged 20-40 years residing in Arkhangelsk, Russia, six months after recovering from COVID-19. The count of leukocytes in the peripheral blood and their differential were evaluated using standard methods to assess the immunological status. To delve deeper into the immunological landscape, phenotypes of lymphocytes (CD5+, CD8+, CD10+, and CD95+) were evaluated using an indirect immunoperoxidase reaction with monoclonal antibodies on dried drop lymphocyte preparations. After incubating blood with latex molecules, the activity and quantity of phagocytes were assessed using a light microscope. The neutrophil/lymphocyte ratio was found to be inverted in the female subjects under investigation. The high concentration of cytotoxic T-lymphocytes (CD8+) and lymphocytes with apoptotic receptors (CD95+) suggests a potential correlation with a concurrent reduction in the expression of the total T-cell marker (CD5+) across all cases. This association was further linked to a decrease in lymphoproliferative activity and a relative decline in phagocytic activity. These findings led us to posit that the total recovery time after COVID-19 might extend beyond six months, indicative of a prolonged impact on the body's protective capacity. Our observations prompt the hypothesis that cellular immunity plays a crucial role in determining the severity of COVID-19 infection. Specifically, individuals with initially robust phagocytic activity may be predisposed to experiencing a milder form of the infection. However, this assumption warrants further investigation and clarification in individuals with moderate and severe disease progression (Tab. 1, Ref. 17). Keywords: arctic, COVID-19, cytotoxic t-lymphocytes, apoptosis, lymphoproliferation, cellular immunity, phagocytic activity.
- Published
- 2024
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34. Single-cell sequencing reveals the evolution of immune molecules across multiple vertebrate species.
- Author
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Jiao A, Zhang C, Wang X, Sun L, Liu H, Su Y, Lei L, Li W, Ding R, Ding C, Dou M, Tian P, Sun C, Yang X, Zhang L, and Zhang B
- Subjects
- Animals, Humans, Mice, Macrophages, Swine, Zebrafish genetics, Adaptive Immunity genetics, Transcriptome, Immunity, Innate genetics
- Abstract
Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates., Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species., Methods: Single-cell RNA sequencing (scRNA-seq)., Results: We uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human., Conclusions: Therefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)
- Published
- 2024
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35. CD4+CCR6+ T cells dominate the BCG-induced transcriptional signature
- Author
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Akul Singhania, Paige Dubelko, Rebecca Kuan, William D. Chronister, Kaylin Muskat, Jyotirmoy Das, Elizabeth J. Phillips, Simon A. Mallal, Grégory Seumois, Pandurangan Vijayanand, Alessandro Sette, Maria Lerm, Bjoern Peters, and Cecilia Lindestam Arlehamn
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Receptors, CCR6 ,Medicine (General) ,Research paper ,BCG ,tuberculosis ,T cell ,Adaptive immunity ,vaccine ,transcriptomics ,CCR6+ T cells ,Receptors, Antigen, T-Cell ,chemical and pharmacologic phenomena ,General Biochemistry, Genetics and Molecular Biology ,R5-920 ,Humans ,Longitudinal Studies ,RNA-Seq ,Gene Expression Profiling ,General Medicine ,DNA Methylation ,Th1 Cells ,Gene Expression Regulation ,BCG Vaccine ,Medicine ,Th17 Cells ,Radiologi och bildbehandling ,Radiology, Nuclear Medicine and Medical Imaging - Abstract
Background: The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Methods: We investigated immune responses in adult individuals pre and 8 months post BCG vaccination. We specifically determined changes in gene expression, cell subset composition, DNA methylome, and the TCR repertoire induced in PBMCs and CD4 memory T cells associated with antigen stimulation by either BCG or a Mycobacterium tuberculosis (Mtb)-derived peptide pool. Findings: Following BCG vaccination, we observed increased frequencies of CCR6+ CD4 T cells, which includes both Th1* (CXCR3+CCR6+) and Th17 subsets, and mucosal associated invariant T cells (MAITs). A large number of immune response genes and pathways were upregulated post BCG vaccination with similar patterns observed in both PBMCs and memory CD4 T cells, thus suggesting a substantial role for CD4 T cells in the cellular response to BCG. These upregulated genes and associated pathways were also reflected in the DNA methylome. We described both qualitative and quantitative changes in the BCG-specific TCR repertoire post vaccination, and importantly found evidence for similar TCR repertoires across different subjects. Interpretation: The immune signatures defined herein can be used to track and further characterize immune responses induced by BCG, and can serve as reference for benchmarking novel vaccination strategies. (C) 2021 The Author(s). Published by Elsevier B.V. Funding Agencies|NIH, USAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [U19 AI118626, S10 RR027366, S10 OD016262]
- Published
- 2021
36. SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity
- Author
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Ida Monrad, Marie H. Pahus, Rune Hartmann, Ole Schmeltz Søgaard, Martin Tolstrup, Jesper Damsgaard Gunst, Christian Erikstrup, Giacomo S. Frattari, Rikke Olesen, Mariane H. Schleimann, Line K. Vibholm, Stine S F Nielsen, Lars Østergaard, Andreas Holleufer, and Jesper F Højen
- Subjects
Male ,0301 basic medicine ,Medicine (General) ,Denmark ,Adaptive Immunity ,CD8-Positive T-Lymphocytes ,Antibodies, Viral ,medicine.disease_cause ,Severity of Illness Index ,Neutralization ,Serology ,0302 clinical medicine ,Medicine ,Coronavirus ,biology ,CD8 T-cell ,General Medicine ,Middle Aged ,Acquired immune system ,Adaptive ,Asymptomatic ,Virus ,030220 oncology & carcinogenesis ,Spike Glycoprotein, Coronavirus ,Female ,Angiotensin-Converting Enzyme 2 ,Antibody ,Research Paper ,Adult ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Young Adult ,03 medical and health sciences ,R5-920 ,Immune system ,Blocking antibody ,Animals ,Humans ,Immune response ,Aged ,Severe ,business.industry ,SARS-CoV-2 ,COVID-19 ,Antibodies, Neutralizing ,030104 developmental biology ,Immunology ,biology.protein ,Corona ,CD8+ T-cell ,business - Abstract
Background: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed.Methods: We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3rd and July 9th 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8+ T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls.Findings: We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2+ individuals.Interpretation: The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity.Funding: This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B)
- Published
- 2021
37. Directs effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on adaptive immunogenesis
- Author
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Galina V. Seledtsova, Ekaterina M. Morozova, Natalja D. Gazatova, Victor I. Seledtsov, M. E. Meniailo, and V. V. Malashchenko
- Subjects
Lipopolysaccharides ,T-Lymphocytes ,030231 tropical medicine ,Immunology ,Adaptive Immunity ,Biology ,Lymphocyte Activation ,Monocytes ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Immunology and Allergy ,Monocytes macrophages ,030212 general & internal medicine ,Cells, Cultured ,Pharmacology ,Macrophages ,Direct effects ,Granulocyte-Macrophage Colony-Stimulating Factor ,Colony-stimulating factor ,Phenotype ,Granulocyte macrophage colony-stimulating factor ,Cytokines ,Research Paper ,medicine.drug - Abstract
Background: We studied direct effects of human granulocyte-macrophage colony stimulating factor (GM-CSF) on phenotypical characteristics and cytokine-production of non-activated and activated human monocytes/macrophages (Mc/Mphs) and T cells. Methods: Purified Mc/Mphs were activated by bacterial lipopolysaccharide (LPS, 1 μg/ml) for 24 h, while T cells were activated by particles conjugated and antibodies (Abs) against human CD2, CD3, and CD28 for 48 h. Results: GM-CSF treatment (0.01–10 ng/ml) was shown to reduce percentages of CD197 (CCR7)-positive cells in non-activated Mph cultures, without affecting significantly CD14(+) (LPS co-receptor), CD16(+) (FcγRIII, low-affinity Fc-receptor), CD119(+) (interferon-gamma receptor 1), and CD124(+) (IL4 receptor α-subunit) cells. In addition, GM-CSF reduced relative numbers of CD197(+) cells, as well as CD14(+), CD16(+), and CD119(+) cells in activated Mph cultures without affecting CD124(+) cell distribution. GM-CSF at the highest dose of 10 ng/ml enhanced TNF-α and IL-6 (but not IL-1β and IL-10) production in activated Mc/Mphs. In activated T cell cultures, GM-CSF at 0.1–1.0 ng/ml augmented CD38(+) cell numbers in naïve СD45RA(+)/СD197(+) and central memory СD45RA(−)/СD197(+) cell subsets, with no effect on effector СD45RA(−)/СD197(−) and terminally differentiated effector СD45RA(+)/СD197(−) cells. GM-CSF at a low dose (0.01 ng/ml) down-regulated INF-γ production, while at a high dosage (10.0 ng/ml) up-regulated IL-2 and IL-4 production. Conclusion: In general, the results suggest that GM-CSF is able to facilitate the implication of both Mph and T cells in the adaptive immunogenesis.
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- 2019
38. Alteration of Adaptive Immunity in a Colorectal Peritoneal Carcinomatosis Model
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Hongming Miao, Xia Kang, Wei Xiang, Rongchen Shi, Lili Zhang, Jinping Wang, and Fengtian He
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0301 basic medicine ,Colorectal cancer ,business.industry ,peritoneal carcinomatosis ,Intraperitoneal inoculation ,colorectal cancer ,Spleen ,adaptive immunity ,medicine.disease ,Acquired immune system ,Colorectal cancer cell line ,Peritoneal carcinomatosis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,business ,Visceral fat ,CD8 ,Research Paper - Abstract
Colorectal cancer (CRC) usually gives rise to transcoelomic spread and ultimately causes peritoneal carcinomatosis (PC). However, mechanism studies, especially the immunological basis of colorectal PC, are rarely revealed due to lack of a suitable PC model. Here we selected a mouse colorectal cancer cell line MC-38 for intraperitoneal inoculation in the C57BL/6 mice to mimic the development of colorectal PC. We demonstrated that the injected CRC cells preferentially and rapidly migrated and colonized in the visceral fat tissues, but not in other visceral organs. With flow cytometric analysis, we found the proportions of spleen T cells and B cells were not affected by PC progression, while the ratios of blood CD4+ and CD8+ T cells were largely influenced. Especially, the quantity or activity of CD4+ and CD8+ T cells in visceral fats were intimately regulated by PC development. Taken together, we successfully constructed a colorectal PC model in immune-competent mice and revealed the alteration of adaptive immunity in PC development. Our study might potentiate the research and therapy strategies of colorectal PC.
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- 2019
39. RIP3 promotes colitis-associated colorectal cancer by controlling tumor cell proliferation and CXCL1-induced immune suppression
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Hai-Jiao Yang, Jian Cui, Zhu-Chun Li, Juan Tang, Ming Zheng, Zhen-Yu Liu, Yi-Ming Li, Zhi-Nan Chen, Jian-Li Jiang, Xin-Yu Fan, Jing-Min Yu, and Jian-Chao Wang
- Subjects
0301 basic medicine ,Myeloid ,Carcinogenesis ,Colon ,MAP Kinase Signaling System ,Chemokine CXCL1 ,T-Lymphocytes ,Necroptosis ,T cell ,IBD ,Gene Expression ,necroptosis ,Medicine (miscellaneous) ,Apoptosis ,colorectal cancer ,Adaptive Immunity ,medicine.disease_cause ,Gene Knockout Techniques ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Animals ,Medicine ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Cell Proliferation ,ulcerative colitis ,Anthracenes ,Tumor microenvironment ,business.industry ,Epithelial Cells ,Colitis ,Mice, Inbred C57BL ,CXCL1 ,030104 developmental biology ,medicine.anatomical_structure ,Tumor progression ,Receptor-Interacting Protein Serine-Threonine Kinases ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Cancer research ,Colorectal Neoplasms ,business ,Signal Transduction ,Research Paper ,RIP3 - Abstract
Rationale: Necroptosis is a programmed form of non-apoptotic cell death that requires receptor-interacting protein 3 (RIP3). RIP3 has been shown to be relevant in multiple tumor types and has differential impact on tumor progression. We investigated whether RIP3 is involved in the progression of colitis-associated cancer (CAC) in mice. Methods: Tissues from colorectal cancer patients were examined for RIP3 expression. CAC was induced using azoxymethane (AOM) injection followed by dextran sodium sulfate (DSS) treatment in RIP3-deficient or wild-type mice. Colon tissues were collected and analyzed by Western blotting and gene expression profile analyses. Immune cell infiltration and CXCL1 expression were examined by flow cytometry and Real-time PCR, respectively. Results: RIP3 expression was upregulated in mouse CAC and human colon cancer. RIP3-deficient mice showed significantly attenuated colitis-associated tumorigenesis. Bone marrow transplantation experiments suggested that RIP3's function in hematopoietic cells primarily contributes to the phenotype. RIP3 supported epithelial proliferation and tumor growth via JNK signaling but had no effect on apoptosis. RIP3 deletion increased T cell accumulation and reduced infiltration by immunosuppressive subsets of myeloid cells during acute colitis and CAC. The immune-suppressive tumor microenvironment was dependent on RIP3-induced expression of the chemokine attractant CXCL1, and administration of recombinant CXCL1 during CAC restored tumorigenesis in Rip3-/- mice. Conclusion: Our results reveal an unexpected function of RIP3 in enhancing the proliferation of premalignant intestinal epithelial cells (IECs) and promoting myeloid cell-induced adaptive immune suppression. These two distinct mechanisms of RIP3-induced JNK and CXCL1 signalling contribute to CAC progression.
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- 2019
40. Correlation Between Stem and Progenitor Cells Number and Immune Response in Patients After Allogeneic Kidney Transplant
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Maciej Kotowski, Karolina Kędzierska-Kapuza, Marek Ostrowski, K. Tejchman, Edyta Paczkowska, Anna Sobuś, Jerzy Sieńko, Ewa Pilichowska, and Jarosław Piątek
- Subjects
Adult ,Male ,T-Lymphocytes ,medicine.medical_treatment ,CD34 ,Adaptive Immunity ,CD38 ,T-Lymphocytes, Regulatory ,Young Adult ,Immune system ,Humans ,Medicine ,Renal Insufficiency, Chronic ,Progenitor cell ,Kidney transplantation ,Aged ,Original Paper ,B-Lymphocytes ,Transplantation ,business.industry ,Stem Cells ,Immunosuppression ,General Medicine ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Haematopoiesis ,Immunology ,Female ,Stem cell ,business - Abstract
BACKGROUND Stem and progenitor cells are of great interest in all medical procedures involving tissue regeneration. There is a consensus that the use of stem cells after solid organ transplantation may play a role in tissue repair and in immunosuppression. The aim of this study was to determine possible relations between stem cell count and the immune response in a group of patients after kidney transplantation. MATERIAL AND METHODS The study was conducted on a group of 100 patients who underwent kidney transplantation. The following phenotypic markers of the studied cell subpopulations were adopted: Treg cells (CD3+CD4+CD25high), circulating hematopoietic cells (CD34+CD133+CD45+CD38-), and non-hematopoietic cells (Lin-CXCR4+CD133-CD45-). Cell subpopulations were assessed using LSRII flow cytometer (BD Biosciences, San Jose, CA, USA). RESULTS Positive correlation was observed between non-hematopoietic stem cells percentage and recipient's platelets count (P=0.04). Moreover, a higher percentage of non-hematopoietic cells was accompanied by lower numbers of B lymphocytes (P=0.03) and Treg cells (P=0.02). CONCLUSIONS Our study revealed significant associations between the intensity of ongoing immune response processes and tissue damage, and the release of stem and progenitor cells into circulation. These findings suggest their role in the stimulation of protective processes in terms of graft regeneration.
- Published
- 2018
41. Identification of an immune checkpoint gene signature that accurately predicts prognosis and immunotherapy response in endometrial carcinoma
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Jiayan Chen, Xin Zhang, Chun-Li Dong, Xiuying Xie, Xiaocui Gao, and Shao-Wen Li
- Subjects
Aging ,Epithelial-Mesenchymal Transition ,DNA Repair ,medicine.medical_treatment ,immune checkpoint genes ,BTLA ,endometrial carcinoma ,Biology ,Gene mutation ,Adaptive Immunity ,Antigens, Neoplasm ,Databases, Genetic ,Carcinoma ,medicine ,Humans ,Survival analysis ,Disease Resistance ,TNFRSF18 ,Gene Expression Profiling ,biomarkers ,Cell Biology ,Immunotherapy ,Gene signature ,medicine.disease ,Immune Checkpoint Proteins ,Prognosis ,Survival Analysis ,Immune checkpoint ,Endometrial Neoplasms ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Mutation ,Cancer research ,Female ,immunotherapy ,Research Paper - Abstract
In this study, we performed a bioinformatics analysis to identify immune checkpoint genes (ICGs) associated with prognosis and the immunotherapeutic response in endometrial carcinoma (EC) patients. We classified 47 ICGs into high, medium, and low expression groups by performing RNA-sequencing data analysis of EC patient samples from The Cancer Genome Atlas (n = 521) and GSE77688 (n = 88) datasets. Univariate Cox regression analysis showed that seven ICGs (VTCN1, TNFRSF18, TNFRSF14, TNFRSF4, CD40LG, TMIGD2, and BTLA) were associated with prognosis in EC patients. Spearman correlation analysis showed that prognosis-related ICGs correlated positively with immunotherapy response factors, including tumor mutation burden (TMB), mismatch repair gene mutations, neoantigens, clinical stages, and adaptive immune resistance pathway genes. We identified a prognostic gene signature of four ICGs (IDO1, CD274, CTLA4, and TNFRSF14) that accurately predicted survival outcomes of EC patients. TIMER database and Kaplan-Meier survival analysis showed that OS among EC patients with low TNFRSF14 expression was significantly shorter than among those with high TNFRSF14 expression. In vitro experiments showed that TNFRSF14 silencing increased the migration and invasiveness of EC cells by promoting epithelial-mesenchymal transition (EMT). Collectively, these findings reveal an immune checkpoint gene signature that accurately predicts survival outcomes and immunotherapeutic responses in EC patients.
- Published
- 2021
42. Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy
- Author
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Lai, Xin, Dreyer, Florian S., Cantone, Martina, Eberhardt, Martin, Gerer, Kerstin F., Jaitly, Tanushree, Uebe, Steffen, Lischer, Christopher, Ekici, Arif, Wittmann, Jürgen, Jäck, Hans-Martin, Schaft, Niels, Dörrie, Jan, and Vera, Julio
- Subjects
RNA, Untranslated ,dendritic cell ,network biology ,systems biology ,chemical and pharmacologic phenomena ,Dendritic Cells ,Adaptive Immunity ,Cancer Vaccines ,I-kappa B Kinase ,MicroRNAs ,Neoplasms ,Cytokines ,Humans ,therapeutic vaccination in cancer ,Immunotherapy ,ddc:610 ,Cells, Cultured ,Research Paper ,Signal Transduction - Abstract
Dendritic cells (DCs) are professional antigen-presenting cells that induce and regulate adaptive immunity by presenting antigens to T cells. Due to their coordinative role in adaptive immune responses, DCs have been used as cell-based therapeutic vaccination against cancer. The capacity of DCs to induce a therapeutic immune response can be enhanced by re-wiring of cellular signalling pathways with microRNAs (miRNAs). Methods: Since the activation and maturation of DCs is controlled by an interconnected signalling network, we deploy an approach that combines RNA sequencing data and systems biology methods to delineate miRNA-based strategies that enhance DC-elicited immune responses. Results: Through RNA sequencing of IKKβ-matured DCs that are currently being tested in a clinical trial on therapeutic anti-cancer vaccination, we identified 44 differentially expressed miRNAs. According to a network analysis, most of these miRNAs regulate targets that are linked to immune pathways, such as cytokine and interleukin signalling. We employed a network topology-oriented scoring model to rank the miRNAs, analysed their impact on immunogenic potency of DCs, and identified dozens of promising miRNA candidates, with miR-15a and miR-16 as the top ones. The results of our analysis are presented in a database that constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (https://www.synmirapy.net/dc-optimization). Conclusions: Our approach enables the systematic analysis and identification of functional miRNA-gene interactions that can be experimentally tested for improving DC immunogenic potency.
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- 2021
43. B and T Lymphocyte Densities Remain Stable With Age in Human Cortex
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Marion S. Buckwalter, Claudia K. Suemoto, Roberta Diehl Rodriguez, Edward D. Plowey, Kacey Berry, Daniela Souza Farias-Itao, Lea T. Grinberg, and Julie A. Schneider
- Subjects
0301 basic medicine ,Adult ,Male ,Aging ,T-Lymphocytes ,brain ,1.1 Normal biological development and functioning ,Inflammation ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Cell Count ,Pilot Projects ,Biology ,Adaptive Immunity ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Clinical Research ,Underpinning research ,Cortex (anatomy) ,medicine ,80 and over ,Humans ,human ,Aged ,Aged, 80 and over ,Cerebral Cortex ,Glial activation ,Original Paper ,B-Lymphocytes ,General Neuroscience ,Inflammatory and immune system ,Neurosciences ,T lymphocyte ,adaptive immunity ,Middle Aged ,Acquired immune system ,Brain Disorders ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Neurological ,Female ,Neurology (clinical) ,medicine.symptom ,immune ,030217 neurology & neurosurgery ,Function (biology) ,RC321-571 - Abstract
One hallmark of human aging is increased brain inflammation represented by glial activation. With age, there is also diminished function of the adaptive immune system, and modest decreases in circulating B- and T-lymphocytes. Lymphocytes traffic through the human brain and reside there in small numbers, but it is unknown how this changes with age. Thus we investigated whether B- and T-lymphocyte numbers change with age in the normal human brain. We examined 16 human subjects in a pilot study and then 40 human subjects from a single brain bank, ranging in age from 44–96 years old, using rigorous criteria for defining neuropathological changes due to age alone. We immunostained post-mortem cortical tissue for B- and T-lymphocytes using antibodies to CD20 and CD3, respectively. We quantified cell density and made a qualitative assessment of cell location in cortical brain sections, and reviewed prior studies. We report that density and location of both B- and T-lymphocytes do not change with age in the normal human cortex. Solitary B-lymphocytes were found equally in intravascular, perivascular, and parenchymal locations, while T-lymphocytes appeared primarily in perivascular clusters. Thus, any change in number or location of lymphocytes in an aging brain may indicate disease rather than normal aging.
- Published
- 2021
44. Editorial: Adaptive immunity in atherosclerosis.
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Slütter, Bram and Ley, Klaus
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AUTOIMMUNE diseases ,ATHEROSCLEROSIS ,REGULATORY T cells ,IMMUNITY ,T-cell exhaustion - Abstract
This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of adaptive immunity in atherosclerosis, a condition that contributes to acute cardiovascular events. The editorial highlights the importance of chronic inflammation in atherosclerosis and the potential for new intervention strategies. It also explores the use of new immunological techniques to study the role of the adaptive immune system in the development, progression, and regression of atherosclerosis. The document includes summaries of several research papers that investigate different aspects of adaptive immunity in atherosclerosis, including T cell and B cell responses. Overall, the editorial provides an overview of the latest findings in this field and serves as a valuable resource for researchers interested in studying adaptive immunity in atherosclerosis. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
45. Spatiotemporal and cell-state control of antigen presentation during tolerance and immunity.
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Hor JL and Germain RN
- Subjects
- Humans, Immune Tolerance, Antigen Presentation, Adaptive Immunity
- Abstract
Effective adaptive immunity is rendered possible by highly organized tissue architecture and coordinated cellular crosstalk. While detailed spatiotemporal analyses of antigen presentation and adaptive immune activation in secondary lymphoid tissues have been a major focus of study, it is clear that antigen presentation in other tissues also plays a critical role in shaping the immune response. In this article, we concentrate on two opposing aspects of adaptive immunity: tolerance and antitumor immunity, to illustrate how a complex set of antigen presentation mechanisms contributes to maintaining a delicate balance between robust immunity and avoidance of autoimmune pathology. We emphasize the importance of how immune cell identity, state, and location collectively determine the nature of adaptive immune responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
46. Investigating the immune mechanism of natural products in the treatment of lung cancer.
- Author
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Lian Yang, Yukun Chen, Kaile Liu, Yuanyuan Chen, Yu Zhang, Zhanxia Zhang, and Hegen Li
- Subjects
NATURAL products ,LUNG cancer ,T cell differentiation ,CELL death ,CANCER treatment ,KILLER cells ,T cells - Abstract
With the deepening of people's understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body's immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
47. New chimeric TLR7/NOD2 agonist is a potent adjuvant to induce mucosal immune responses
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Laura Papagno, Stéphane Paul, Nicolas Rochereau, Alice Gutjahr, Eric Perouzel, Victor Appay, Bernard Verrier, Thierry Lioux, Fabienne Vernejoul, Fabienne Jospin, Blandine Chanut, Gestionnaire, Hal Sorbonne Université, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), InvivoGen Europe, Kumamoto University, Université Jean Monnet [Saint-Étienne] (UJM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne)
- Subjects
0301 basic medicine ,Research paper ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Nod2 Signaling Adaptor Protein ,lcsh:Medicine ,Pharmacology ,Adaptive Immunity ,CD8-Positive T-Lymphocytes ,Mice ,0302 clinical medicine ,HIV vaccine ,Receptor ,TLR7 ,AIDS Vaccines ,lcsh:R5-920 ,biology ,Chemistry ,Pattern recognition receptor ,virus diseases ,General Medicine ,3. Good health ,[SDV] Life Sciences [q-bio] ,030220 oncology & carcinogenesis ,Female ,lcsh:Medicine (General) ,Adjuvant ,Agonist ,medicine.drug_class ,Antigen presentation ,General Biochemistry, Genetics and Molecular Biology ,NOD2 ,Cell Line ,03 medical and health sciences ,Adjuvants, Immunologic ,MHC class I ,medicine ,Animals ,Humans ,Adjuvants ,Administration, Intranasal ,lcsh:R ,Immunity, Humoral ,030104 developmental biology ,Toll-Like Receptor 7 ,biology.protein ,Chimeric ,Vaccine ,HeLa Cells - Abstract
Background PRR (Pattern Recognition Receptor) agonists have been widely tested as potent vaccine adjuvants. TLR7 (Toll-Like Receptor 7) and NOD2 (nucleotide-binding oligomerization domain 2) are key innate receptors widely expressed at mucosal levels. Methods Here, we evaluated the immunostimulatory properties of a novel hybrid chemical compound designed to stimulate both TLR7 and NOD2 receptors. Finding The combined TLR7/NOD2 agonist showed increase efficacy than TLR7L or NOD2L agonists alone or combined in different in vitro models. Dual TLR7/NOD2 agonist efficiently stimulates TLR7 and NOD2, and promotes the maturation and reprogramming of human dendritic cells, as well as the secretion of pro-inflammatory or adaptive cytokines. This molecule also strongly induces autophagy in human cells which is a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. In vivo, TLR7/NOD2L agonist is a potent adjuvant after intranasal administration with NP-p24 HIV vaccine, inducing high-quality humoral and adaptive responses both in systemic and mucosal compartments. Use of TLR7/NOD2L adjuvant improves very significantly the protection of mice against an intranasal challenge with a vaccinia virus expressing the p24. Interpretation Dual TLR7/NOD2L agonist is a very potent and versatile vaccine adjuvant and promote very efficiently both systemic and mucosal immunity. Funding This work was supported by Sidaction .
- Published
- 2020
48. Differences in C-type lectin receptors and their adaptor molecules in the peritoneal fluid of patients with endometriosis and gynecologic cancers
- Author
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Yong Sung Won, Dong Choon Park, Seung Geun Yeo, and Sang Hoon Kim
- Subjects
Adult ,Genital Neoplasms, Female ,Endometriosis ,Enzyme-Linked Immunosorbent Assay ,Adaptive Immunity ,Immunoglobulin secretion ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,C-type lectin ,Immunoglobulin ,medicine ,Ascitic Fluid ,Humans ,Lectins, C-Type ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Gynecologic cancer ,Receptor ,B cell ,Galectin ,B-Lymphocytes ,030219 obstetrics & reproductive medicine ,business.industry ,Peritoneal fluid ,General Medicine ,Middle Aged ,medicine.disease ,Immunoglobulin A ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Immunoglobulin M ,Immunoglobulin G ,030220 oncology & carcinogenesis ,Cancer research ,Female ,C-type lectin receptors ,business ,Research Paper - Abstract
Endometriosis, although not malignant, has clinically demonstrated properties of invasiveness and metastasis. The pathogenesis of endometriosis, however, has not yet been elucidated. The immunological differences between endometriosis and malignant gynecologic tumors were analyzed by assessing C-type lectin receptors, which are associated with innate immunity, and immunoglobulin secretion, which is associated with B cell adaptive immunity, in the peritoneal fluid of these patients. Peritoneal fluid samples were obtained from 42 patients with benign masses (control group), 38 with endometriosis, and 43 with gynecologic (ovarian, uterine, and cervical) cancers. The levels of expression in these samples of mRNAs encoding the C-type lectin receptors Dectin-1, MR1, MR2, DC-SIGN, Syk, Card 9, Bcl 10, Malt 1, src, Dec 205, Galectin, Tim 3, Trem 1, and DAP 12, were measured by real-time reverse transcription polymerase chain reaction, and the concentrations of IgG, IgA and IgM were measured by enzyme-linked immunosorbent assays (ELISA). Findings in the three groups were compared. The level of galectin mRNA was significantly lower, and the levels of MR2 and DAP 12 mRNAs significantly higher, in the endometriosis than in the control group (p0.05). C-type lectin receptors and immunoglobulins act cooperatively and are closely associated in the pathogenesis of endometriosis. The decreased expression of galectin mRNA in the peritoneal fluid of the endometriosis group suggests that endometriosis and gynecologic cancers have similar immunologic characteristics.
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- 2018
49. Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression
- Author
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Clarissa von Haefen, Johannes Kurth, Gunnar Lachmann, Claudia Spies, and Fatima Yuerek
- Subjects
0301 basic medicine ,Male ,Time Factors ,medicine.medical_treatment ,T cell ,Adaptive Immunity ,Monocytes ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Pancreatectomy ,Postoperative Complications ,Immunity ,Immune Tolerance ,Medicine ,Cytotoxic T cell ,Humans ,Lymphocyte Count ,Lymphocytes ,innate immunity ,monocytic function ,T cell function ,Aged ,Retrospective Studies ,Innate immune system ,business.industry ,Immunosuppression ,General Medicine ,Middle Aged ,Acquired immune system ,Immunity, Innate ,acquired immunity ,Esophagectomy ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,Cytokines ,Female ,immune suppression ,business ,Research Paper - Abstract
Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed. Innate and acquired immune cells, the expression of human leukocyte antigen-D related on monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-α and IL-10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after surgery (pod5). Recovery of immune cells was defined by a significant decrease respectively increase after a significant postoperative alteration. Statistical analyses were performed using nonparametric statistical procedures. Results: Postoperative alterations of innate immune cells recovered on pod2 (eosinophils), pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-α and IL-10 secretion), whereas alterations of acquired immune cells (lymphocytes, T cells, T helper cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T cells showed an impaired production of the T helper (Th) 1 cytokine IFN-γ upon Con A stimulation on pod1, while Th2 specific cytokine release did not change until pod5. Conclusions: Innate immunity recovered earlier than acquired immunity during severe postoperative immunosuppression. Furthermore, we found a more anti- than pro-inflammatory T cell function on the first day after surgery, while T cell counts decreased.
- Published
- 2018
50. CXCL14 Acts as a Specific Carrier of CpG DNA into Dendritic Cells and Activates Toll-like Receptor 9-mediated Adaptive Immunity
- Author
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Rena Takahashi, Naoto Naruse, Rina Iwase, Kohei Tsuji, Akira Shigenaga, Hideko Nuriya, Takahiko Hara, Akira Otaka, and Kosuke Tanegashima
- Subjects
0301 basic medicine ,Endosome ,CpG Oligodeoxynucleotide ,lcsh:Medicine ,chemical and pharmacologic phenomena ,Endosomes ,Adaptive Immunity ,General Biochemistry, Genetics and Molecular Biology ,TLR9 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Animals ,CXCL14 ,lcsh:R5-920 ,CpG DNA ,Interleukin-12 Subunit p40 ,Chemistry ,lcsh:R ,hemic and immune systems ,Dendritic Cells ,General Medicine ,Acquired immune system ,Toll-Like Receptor 9 ,Immunosurveillance ,030104 developmental biology ,Gene Expression Regulation ,Oligodeoxyribonucleotides ,CpG site ,Cancer research ,lcsh:Medicine (General) ,Lysosomes ,Chemokines, CXC ,Research Paper ,030215 immunology - Abstract
CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs. Consistent with this, ODN2395-mediated activation of DCs was significantly attenuated in Cxcl14-knockout mice. CXCL14 bound CpG ODN with high affinity at pH 7.5, but not at pH 6.0, thereby enabling efficient delivery of CpG ODN to TLR9 in the endosome/lysosome. Furthermore, the CXCL14-CpG ODN complex specifically bound to high affinity CXCL14 receptors on DCs. Thus, CXCL14 serves as a specific carrier of CpG DNA to sensitize TLR9-mediated immunosurveillance., Highlights • CXCL14 specifically binds CpG DNA with high affinity. • CXCL14/CpG DNA complex is efficiently transported into dendritic cells. • CXCL14/CpG DNA induces cytokine production via Toll-like receptor 9. We discovered that CXCL14 specifically binds CpG DNAs with high affinity and transports them into the endosomes and lysosomes of dendritic cells (DCs). Consequently, Toll-like receptor 9 (Tlr9) in DCs was activated, thereby leading to robust production of IL-12 p40 and IL-6. These activities of CXCL14 were not observed in Tlr9-deficient DCs. Moreover, CpG DNA (ODN2395)-mediated activation of DCs was significantly attenuated in Cxcl14-knockout mice. Therefore, CXCL14 plays an important role in the Tlr9-mediated immunosurveillance against pathogens and cancers. From the clinical point of view, CXCL14/CpG DNA could be useful as a new type of vaccine adjuvant.
- Published
- 2017
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