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Immunology is a rapidly advancing and expanding field that is regularly highlighted in the lay media, whether it be checkpoint blockade immunotherapy winning the Nobel Prize, CAR-T cells in the treatment of cancer, or the latest anti-inflammatory/immunomodulatory medication advertised directly to consumers. Advances such as these not only transform the way we think about immunology, they also illuminate how knowledge of the immune system can be harnessed to impact public health. Immunology is also a vast subject, with thousands of articles published each year that contribute to our understanding of complex processes such as inflammation, pathogen recognition, and self-tolerance, Taken together, these observations pose significant challenges to teaching immunology in the undergraduate classroom. To meet this challenge, instructors can use primary literature as a means to introduce cutting-edge discoveries that have not yet found their way into textbooks, link what students are learning to what they are exposed to in lay media, and ultimately provide added depth to the students' understanding of the immune system all while illustrating how clinical advances are fundamentally dependent on basic research studies. Furthermore, the addition of primary literature to the curriculum can enhance student enthusiasm for learning immunology and can provide an excellent platform for students to gain critical thinking and analytical skills. Presented here are strategies, challenges, and opportunities in the use of primary literature to effectively augment the immunology curriculum in the undergraduate classroom. Topics include selecting papers to read, teaching students how to read scientific literature, and assessing student learning. [ABSTRACT FROM AUTHOR]

Keywords: inner ear; immunology; neuroimmunology; balance; hearing; disorders EN inner ear immunology neuroimmunology balance hearing disorders N.PAG N.PAG 6 02/11/21 20210209 NES 210209 Although the term was first officially used in 1982 ([1]), neuroimmunology is now a mature field that has gained immense traction in the past decade. Similarly, the paper "Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study", describes immune cells (mainly macrophages and to a lesser extent T lymphocytes) associated with the human cochlea and endolymphatic sac (Liu et al.). Moreover, the endolymphatic sac, which is involved in endolymph reabsorption and displays morphological changes in MD ([43]), is the primary immune structure of the inner ear ([44]), and inner ear vasculature permeability is strongly affected by inflammation ([45]). Footnotes 1 PUBMED search with the query "(inner ear OR cochlea OR vestibular) AND (neuroimmune OR neuroimmunology)" only retrieves 14 results, but this reflects the still sparse use of "neuroimmune", since the related queries "(inner ear OR cochlea OR vestibular) AND (immune OR macrophage OR cytokine)" and "(inner ear OR cochlea OR vestibular) AND (inflammatory OR inflammation)" retrieve 1,734 and 2,043 results, respectively. [Extracted from the article]

Psoriasis is a recurring inflammatory skin condition characterized by scaly, red patches on the skin. It affects approximately 3% of the US population and is associated with histological changes such as epidermal hyperplasia, increased blood vessel proliferation, and infiltration of leukocytes into the skin's dermis. T cells, which are classified into various subtypes, have been found to play significant roles in immune-mediated diseases, particularly psoriasis. This paper provides a review of the different T lymphocyte subtypes and their functions in psoriasis, as well as an overview of targeted therapies for treating psoriasis. [ABSTRACT FROM AUTHOR]

Immunotherapy has changed the treatment strategy of non-small cell lung cancer (NSCLC) in recent years, among which anti-PD-1/PD-L1 antibodies are the most used. However, the majority of patients with NSCLC do not derive benefit from immune checkpoint inhibitors (ICIs). Vascular abnormalities are a hallmark of most solid tumors and facilitate immune evasion. Thus, combining antiangiogenic therapies might increase the effectiveness of anti-PD-1/PD-L1 antibodies. In this paper, the mechanisms of anti-angiogenic agents combined with anti-PD-1/PD-L1 antibodies are illustrated, moreover, relevant clinical studies and predictive immunotherapeutic biomarkers are summarized and analyzed, in order to provide more treatment options for NSCLC patients. [ABSTRACT FROM AUTHOR]

The opinion flows from Introduction to the immunological quantum that requires a historical perspective, to Quantum vaccine algorithms supported by a bibliometric analysis, to Quantum vaccinomics describing from our perspective the different vaccinomics and quantum vaccinomics algorithms. Finally, in the Discussion and conclusions we propose novel platforms and algorithms developed to further advance on quantum vaccinomics. In the paper we refer to protective epitopes or immunological quantum for the design of candidate vaccine antigens, which may elicit a protective response through both cellular and antibody mediated mechanisms of the host immune system. Vaccines are key interventions for the prevention and control of infectious diseases affecting humans and animals worldwide. Biophysics led to quantum biology and quantum immunology reflecting quantum dynamics within living systems and their evolution. In analogy to quantum of light, immune protective epitopes were proposed as the immunological quantum. Multiple quantum vaccine algorithms were developed based on omics and other technologies. Quantum vaccinomics is the methodological approach with different platforms used for the identification and combination of immunological quantum for vaccine development. Current quantum vaccinomics platforms include in vitro, in music and in silico algorithms and top trends in biotechnology for the identification, characterization and combination of candidate protective epitopes. These platforms have been applied to different infectious diseases and in the future should target prevalent and emerging infectious diseases with novel algorithms. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of endogenous danger signals, also known as damage-associated molecular patterns (DAMPs) or alarmins, in cancer immunology and immunotherapy. The editorial highlights the impact of these molecules on immune responses and their involvement in cancer immunity. The document also mentions that several articles have been published in the journal on this topic, covering various aspects of endogenous danger signals in cancer immunology and immunotherapy. The editorial concludes by emphasizing the potential of this research to guide the development of precision cancer immunotherapies. [Extracted from the article]

Diabetes mellitus (DM) has been frequently associated with an impaired immune response against infectious agents, making affected patients at risk for more severe disease and sometimes causing worse outcomes. The recent COVID-19 pandemic has seriously affected patients with both diabetes, in particular those carrying comorbidities or with poor glycemic control. As regards pediatric diabetes mellitus, the availability of more accurate and technological tools for glycemic management and the improved markers of metabolic control might mitigate the negative impact of infections. Notably, good metabolic control of diabetes since its diagnosis reduces not only the risk of microangiopathic complications but also of impaired immune response to infectious diseases. Therefore, vaccinations are strongly recommended. Our paper aims to provide the most updated evidence regarding infectious diseases in type 1 pediatric DM. [ABSTRACT FROM AUTHOR]

Sepsis is an unsolved clinical condition with a substantial mortality rate in the hospital. Despite decades of research, no effective treatments for sepsis exists. The role of adenosine in the pathogenesis of sepsis is discussed in this paper. Adenosine is an essential endogenous molecule that activates the A1, A2a, A2b, and A3 adenosine receptors to regulate tissue function. These receptors are found on a wide range of immune cells and bind adenosine, which helps to control the immune response to inflammation. The adenosine receptors have many regulatory activities that determine the onset and progression of the disease, which have been discovered via the use of animal models. A greater understanding of the role of adenosine in modulating the immune system has sparked hope that an adenosine receptor-targeted treatment may be used one day to treat sepsis. [ABSTRACT FROM AUTHOR]

Cancer is a major threat to human health because of its high mortality, easy recurrence, strong invasion, and metastasis. Photodynamic therapy (PDT) is a promising minimally invasive treatment for tumor. Compared with traditional treatment methods, PDT is less invasive and does not easily damage normal tissues. Most of the effects of this treatment are due to the direct effects of singlet oxygen together with reactive oxygen species. PDT can provide the source of active oxygen for the Fenton reaction, which enhances ferroptosis and also improves the efficacy of PDT in antitumor therapy. Additionally, in contrast to chemotherapy and radiotherapy, PDT has the effect of stimulating the immune response, which can effectively induce immunogenic cell death (ICD) and stimulate immunity. PDT is an ideal minimally invasive treatment method for tumors. In this paper, according to the characteristics of anti-tumor immunity of PDT, some tumor treatment strategies of PDT combined with anti-tumor immunotherapy are reviewed. [ABSTRACT FROM AUTHOR]

One of the most interesting biological models is that of snail–trematode interactions, many of which ultimately result in the transmission of several important diseases, particularly in the tropics. Herein, we review the scientific advances on a trematode–snail system in which certain populations of Pseudosuccinea columella (a common host species for trematodes) have been demonstrated naturally-resistant to Fasciola hepatica , in association with an effective encapsulation of the parasite by innate immune cells of the host, the hemocytes. Emphasis is made on the molecular and immunological features characterizing each P. columella phenotype in relation to their anti-parasitic competence, their distinctive ecological patterns and the existence of a significant cost of resistance. An integrative overview of the resistance to F. hepatica through comparative immunobiology, genetics and ecology is presented to hypothesize on the possible origins and evolution of this phenomenon and to postulate significant roles for parasite mediated-selection and environmental factors in shaping and maintaining the resistant phenotype in the field. Lastly, clues into future experimental perspectives to deeply characterize the interplay between P. columella and F. hepatica and the immunobiology of the resistance are also included. The advances revised in the present paper are only beginning to unravel mechanisms of anti-parasite innate defense responses and their evolutionary bases, and can facilitate the development of prospective approaches towards practical applications of P. columella resistance. [ABSTRACT FROM AUTHOR]

In the past few years, huge advances have been made in techniques to analyse cells at an individual level using RNA sequencing, and many of these have precipitated exciting discoveries in the immunology of type 1 diabetes (T1D). This review will cover the first papers to use scRNAseq to characterise human lymphocyte phenotypes in T1D in the peripheral blood, pancreatic lymph nodes and islets. These have revealed specific genes such as IL-32 that are differentially expressed in islet –specific T cells in T1D. scRNAseq has also revealed wider gene expression patterns that are involved in T1D and can predict its development even predating autoantibody production. Single cell sequencing of TCRs has revealed V genes and CDR3 motifs that are commonly used to target islet autoantigens, although truly public TCRs remain elusive. Little is known about BCR repertoires in T1D, but scRNAseq approaches have revealed that insulin binding BCRs commonly use specific J genes, share motifs between donors and frequently demonstrate poly-reactivity. This review will also summarise new developments in scRNAseq technology, the insights they have given into other diseases and how they could be leveraged to advance research in the type 1 diabetes field to identify novel biomarkers and targets for immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: Inflammatory bowel diseases (IBDs) are complex chronic inflammatory disorders of the gastro-intestinal (GI) tract with uncertain etiology. IBDs comprise two idiopathic disorders: Crohn's disease (CD) and ulcerative colitis (UC). The aetiology, severity and progression of such disorders are still poorly understood but thought to be influenced by multiple factors (including genetic, environmental, immunological, physiological, psychological factors and gut microbiome) and their interactions. The overarching aim of this review is to evaluate the extent and nature of the interrelationship between these factors with the disease course. A broader conceptual and longitudinal framework of possible neuro-visceral integration, core microbiome analysis and immune modulation assessment may be useful in accurately documenting and characterizing the nature and temporal continuity of crosstalk between these factors and the role of their interaction (s) in IBD disease activity. Characterization of these interactions holds the promise of identifying novel diagnostic, interventions, and therapeutic strategies. Material and Methods: A search of published literature was conducted by exploring PubMed, EMBASE, MEDLINE, Medline Plus, CDSR library databases. Following search terms relating to key question were set for the search included: "Inflammatory bowel diseases," "gut microbiota," "psychological distress and IBD," "autonomic reactivity and IBD," "immune modulation," "chronic inflammation," "gut inflammation," "enteric nervous system," "gut nervous system," "Crohn's disease," "Ulcerative colitis", "depression and IBD", "anxiety and IBD", "quality of life in IBD patients," "relapse in IBDs," "remission in IBDs," "IBD disease activity," "brain-gut-axis," "microbial signature in IBD," "validated questionnaires in IBD," "IBD activity indices," "IBD aetiology," "IBDs and stress," "epidemiology of IBDs", "autonomic nervous system and gut inflammation", "IBD and environment," "genetics of IBDs," "pathways of immune response in IBDs," "sleep disturbances in IBD," "hypothalamic-pituitary-adrenal axis (HPA)," "sympatho-adrenal axis," "CNS and its control of gut function" "mucosal immune response," "commensal and pathogenic bacteria in the gut," "innate and adaptive immunity." Studies evaluating any possible associations between gut microbiome, psychological state, immune modulation, and autonomic function with IBDs were identified. Commonly cited published literatures with high quality research methodology/results and additional articles from bibliographies of recovered papers were examined and included where relevant. Results: Although there is a substantial literature identifying major contributing factors with IBD, there has been little attempt to integrate some factors over time and assess their interplay and relationship with IBD disease activity. Such contributing factors include genetic and environmental factors, gut microbiota composition and function, physiological factors, psychological state and gut immune response. Interdependences are evident across psychological and biological factors and IBD disease activity. Although from the available evidence, it is implausible that a single explanatory model could elucidate the interplay between such factors and the disease course as well as the sequence of the effect during the pathophysiology of IBD. Conclusion: Longitudinal monitoring of IBD patients and integrating data related to the contributing/risk factors including psychological state, physiological conditions, inflammatory/immune modulations, and microbiome composition/function, could help to explain how major factors associate and interrelate leading to exacerbation of symptoms and disease activity. Identifying the temporal trajectory of biological and psychosocial disturbances may also help to assess their effects and interdependence on individuals' disease status. Moreover, this allows greater insight into understanding the temporal progressions of subclinical events as potential ground for disease severity in IBD. Furthermore, understanding the interaction between these risk factors may help better interventions in controlling the disease, reducing the costs related to disease management, further implications for clinical practice and research approaches in addition to improving patients' mental health and quality of life. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic underscores the critical need to integrate immunomics within the One Health framework to effectively address zoonotic diseases across humans, animals, and environments. Employing advanced high-throughput technologies, this interdisciplinary approach reveals the complex immunological interactions among these systems, enhancing our understanding of immune responses and yielding vital insights into the mechanisms that influence viral spread and host susceptibility. Significant advancements in immunomics have accelerated vaccine development, improved viral mutation tracking, and broadened our comprehension of immune pathways in zoonotic transmissions. This review highlights the role of animals, not merely as carriers or reservoirs, but as essential elements of ecological networks that profoundly influence viral epidemiology. Furthermore, we explore how environmental factors shape immune response patterns across species, influencing viral persistence and spillover risks. Moreover, case studies demonstrating the integration of immunogenomic data within the One Health framework for COVID-19 are discussed, outlining its implications for future research. However, linking humans, animals, and the environment through immunogenomics remains challenging, including the complex management of vast amounts of data and issues of scalability. Despite challenges, integrating immunomics data within the One Health framework significantly enhances our strategies and responses to zoonotic diseases and pandemic threats, marking a crucial direction for future public health breakthroughs. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by progressive fibrosis, leading to impaired gas exchange and high mortality. The etiology of IPF is complex, with potential links to autoimmune disorders such as hypothyroidism. This study explores the relationship between hypothyroidism and IPF, focusing on the mediating role of plasma proteins. Methods: A two-sample Mendelian randomization (MR) approach was employed to determine the impact of hypothyroidism on IPF and the mediating role of 4,907 plasma proteins, all in individuals of European ancestry. Sensitivity analyses, external validation, and reverse causality tests were conducted to ensure the robustness of the findings. Additionally, the function of causal SNPs was evaluated through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Conclusion: The findings suggest that hypothyroidism, through altered plasma protein expression, particularly CXCL10, may contribute to the pathogenesis of IPF. This novel insight highlights the potential of CXCL10 as a therapeutic target in IPF, especially in patients with hypothyroidism. The study emphasizes the need for further research into the complex interplay between autoimmune disorders and IPF, with a view towards developing targeted interventions for IPF management. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology hallmarked predominantly by mucocutaneous lesions and ocular involvement. BD shares some common features with autoimmune and autoinflammatory diseases and spondyloarthropathies (MHC-I-opathies). It is related to more than one pathogenic pathway triggered by environmental factors such as infectious agents in genetically predisposed subjects. The interplay between genetic background and immune system is linked to the BD presentation. Genetic factors have been investigated extensively, and several recent genome-wide association studies have confirmed HLA-B * 51 to be the strongest genetic susceptibility factor. However, new non-HLA susceptibility genes have been identified. Genetic variations in the genes encoding the cytokines could affect their function and be associated with disease susceptibility. Infectious agents such as Streptococcus sanguinis or the differences in salivary or gut microbiome composition can be considered to trigger the innate-derived inflammation, which is, subsequently, sustained by adaptive immune responses. Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by HLA-B * 51 , may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in organs affected by the disease. Association with HLA-B * 51 and increased IL-17 response seems to have an important role in neutrophil activity. In this paper, we provide an overview of the most recent advances on BD etiopathogenesis. [ABSTRACT FROM AUTHOR]

Model organisms are often used in biological, medical and environmental research. Among insects, Drosophila melanogaster, Galleria mellonella, Apis mellifera, Bombyx mori, Periplaneta americana , and Locusta migratoria are often used. However, new model organisms still appear. In recent years, an increasing number of insect species has been suggested as model organisms in life sciences research due to their worldwide distribution and environmental significance, the possibility of extrapolating research studies to vertebrates and the relatively low cost of rearing. Beetles are the largest insect order, with their representative – Tribolium castaneum – being the first species with a completely sequenced genome, and seem to be emerging as new potential candidates for model organisms in various studies. Apart from T. castaneum , additional species representing various Coleoptera families, such as Nicrophorus vespilloides, Leptinotarsa decemlineata, Coccinella septempunctata, Poecilus cupreus, Tenebrio molitor and many others, have been used. They are increasingly often included in two major research aspects: biomedical and environmental studies. Biomedical studies focus mainly on unraveling mechanisms of basic life processes, such as feeding, neurotransmission or activity of the immune system, as well as on elucidating the mechanism of different diseases (neurodegenerative, cardiovascular, metabolic, or immunological) using beetles as models. Furthermore, pharmacological bioassays for testing novel biologically active substances in beetles have also been developed. It should be emphasized that beetles are a source of compounds with potential antimicrobial and anticancer activity. Environmental-based studies focus mainly on the development and testing of new potential pesticides of both chemical and natural origin. Additionally, beetles are used as food or for their valuable supplements. Different beetle families are also used as bioindicators. Another important research area using beetles as models is behavioral ecology studies, for instance, parental care. In this paper, we review the current knowledge regarding beetles as model organisms and their practical application in various fields of life science. [ABSTRACT FROM AUTHOR]

Increased interest in the immune system's involvement in pathophysiological phenomena coupled with decreased DNA sequencing costs have led to an explosion of antibody and T cell receptor sequencing data collectively termed "adaptive immune receptor repertoire sequencing" (AIRR-seq or Rep-Seq). The AIRR Community has been actively working to standardize protocols, metadata, formats, APIs, and other guidelines to promote open and reproducible studies of the immune repertoire. In this paper, we describe the work of the AIRR Community's Data Representation Working Group to develop standardized data representations for storing and sharing annotated antibody and T cell receptor data. Our file format emphasizes ease-of-use, accessibility, scalability to large data sets, and a commitment to open and transparent science. It is composed of a tab-delimited format with a specific schema. Several popular repertoire analysis tools and data repositories already utilize this AIRR-seq data format. We hope that others will follow suit in the interest of promoting interoperable standards. [ABSTRACT FROM AUTHOR]

HCV represents a global health problem with ~200 million individuals currently infected, worldwide. With the high cost of antiviral therapies, the global burden of chronic hepatitis C infection (CHCV) infection will be substantially reduced by the development of an effective vaccine for HCV. The field of HCV vaccines is generally divided into proponents of strategies to induce neutralizing antibodies (NAb) and those who propose to elicit cell mediated immunity (CMI). However, for a hepatitis C virus (HCV) vaccine to be effective in preventing infection, it must be capable of generating cross-reactive CD4+, CD8+ T cell, and NAb responses that will cover the major viral genotypes. Simulation models of hepatitis C have predicted that a vaccine of even modest efficacy and coverage will significantly reduce the incidence of hepatitis C. A HCV virus like particle (VLP) based vaccine would fulfill the requirement of delivering critical conformational neutralizing epitopes in addition to providing HCV specific CD4+ and CD8+ epitopes. Several approaches have been reported including insect cell-derived genotype 1b HCV VLPs; a human liver-derived quadrivalent genotype 1a, 1b, 2, and 3a vaccine; a genotype 1a HCV E1 and E2 glycoprotein/MLV Gag pseudotype VLP vaccine; and chimeric HBs-HCV VLP vaccines. All to result in the production of cross-NAb and/or T cell responses against HCV. This paper summarizes the evidence supporting the development of a HCV VLP based vaccine. [ABSTRACT FROM AUTHOR]

Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application ofmicrobial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications. [ABSTRACT FROM AUTHOR]

This article is an editorial that provides an overview of the role of extracellular vesicles (EVs) in mediating cellular communication and their implications for chronic diseases. It discusses the potential of EVs for diagnostic and therapeutic applications and highlights the latest advances in EVs and immunology research. The article includes 11 expert-written articles covering topics such as the impact of macrophage secretomes on spinal cord injuries, the involvement of EVs in psoriasis, and the roles of exosomes in rheumatoid arthritis and autoimmune skin disorders. The document is a compilation of reviews on the potential applications of EVs in various fields, including clinical therapies for neurodegenerative diseases, lung cancer, and diabetes. It emphasizes the need for further research to optimize the use of EVs in clinical settings and highlights their potential in advancing treatment options for chronic diseases. [Extracted from the article]

This article provides an overview of recent advancements in veterinary cancer immunology, focusing on how the immune system interacts with animal cancer cells. It discusses novel immunotherapeutic approaches, such as cancer vaccines and monoclonal antibodies, that have shown promise in treating canine cancers. Comparative oncology, which examines cancer across different species, is highlighted as a valuable approach for identifying common mechanisms and potential treatments. The article also mentions the potential of chimeric antigen receptors (CARs) in veterinary immuno-oncology, although their use in veterinary medicine is still under development. The document is a collection of research articles covering various topics related to cancer treatment in animals, providing new insights and potential therapeutic strategies for veterinary oncology. Ongoing research in this field is crucial for improving cancer management and treatment options for dogs. [Extracted from the article]

In the field of breast cancer treatment, the immunotherapy involving natural killer (NK) cells is increasingly highlighting its distinct potential and significance. Members of the interleukin (IL) family play pivotal regulatory roles in the growth, differentiation, survival, and apoptosis of NK cells, and are central to their anti-tumor activity. These cytokines enhance the ability of NK cells to recognize and eliminate tumor cells by binding to specific receptors and activating downstream signaling pathways. Furthermore, interleukins do not function in isolation; the synergistic or antagonistic interactions between different interleukins can drive NK cells toward various functional pathways, ultimately leading to diverse outcomes for breast cancer patients. This paper reviews the intricate relationship between NK cells and interleukins, particularly within the breast cancer tumor microenvironment. Additionally, we summarize the latest clinical studies and advancements in NK cell therapy for breast cancer, along with the potential applications of interleukin signaling in these therapies. In conclusion, this article underscores the critical role of NK cells and interleukin signaling in breast cancer treatment, providing valuable insights and a significant reference for future research and clinical practice.

This article, titled "Editorial: Women in cancer immunity and immunotherapy," discusses the contributions and challenges faced by women scientists in the field of cancer immunity and immunotherapy. It highlights the achievements of women scientists throughout history and acknowledges the gender gap that still exists in the field. The article also presents several original research articles and reviews that focus on various aspects of cancer immunity and immunotherapy. Overall, the article aims to encourage more women to pursue careers in scientific research and contribute to the advancement of the field. [Extracted from the article]

It is widely acknowledged that the human immune system plays a crucial role in preventing the formation and progression of innumerable types of cancer (1). The mechanisms by which this occurs are numerous, including contributions from both the innate and adaptive immune systems. As such, immunotherapy has long been believed to be an auspicious solution in the treatment of malignancy (2). Recent research has highlighted the promise of natural killer (NK) cells as a more directed immunotherapy approach. This paper will focus on the methods of potentiation of NK cells for their use in cancer therapy. [ABSTRACT FROM AUTHOR]

Helminths and their products can suppress the host immune response to escape host defense mechanisms and establish chronic infections. Current studies indicate that macrophages play a key role in the immune response to pathogen invasion. They can be polarized into two distinct phenotypes: M1 and M2. The present paper examines the impact of the adult Hymenolepis diminuta (HD) tapeworm and its excretory/ secretory products (ESP) on THP-1 macrophages. Monocytes were differentiated into macrophages and cultured with a living parasite or its ESP. Our findings indicate that HD and ESP have a considerable impact on human THP-1 macrophages. Macrophages treated with parasite ESP (with or without LPS) demonstrated reduced expression of cytokines (i.e., IL-1α, TNFα, TGFβ, IL-10) and chemokines (i.e., IL-8, MIP-1α, RANTES, and IL-1ra), while s-ICAM and CxCL10 expression rose after ESP stimulation. In addition, inflammatory factor expression rose significantly when macrophages were exposed to living parasites. Regarding induced and repressed pathways, significant differences were found between HD and ESP concerning their influence on the phosphorylation of ERK1/2, STAT2, STAT3, AMPKα1, Akt 1/2/3 S473, Hsp60, and Hck. The superior immunosuppressive properties of ESP compared to HD were demonstrated with lower levels of IL-1β, TNF-α, IL-6, IL-23, and IL-12p70 following stimulation. The presence of HD and its ESP were found to stimulate mixed M1/M2 macrophage phenotypes. Our findings indicate new molecular mechanisms involved in the response of human macrophages to tapeworm infection, this could be a valuable tool in understanding the mechanisms underlying the processes of immune regulation during cestodiasis. [ABSTRACT FROM AUTHOR]

Highlights from the article: In their original article, Jackson et al. explore whether T cell responsiveness to a range of CMV proteins is different in younger and older healthy people and whether relaxation of anti-CMV immunosurveillance in later life could contribute to disease. Heightened chronic inflammatory status is also likely to affect innate immune cells as well as the T and B cell effects discussed by Frasca and Blomberg. 3 Nikolich-Zugich J, van Lier RAW, Cytomegalovirus (CMV) research in immune senescence comes of age: overview of the 6th InternationalWorkshop on CMV and Immunosenescence.

Major histocompatibility complex Class II (MHCII) proteins initiate and regulate immune responses by presentation of antigenic peptides to CD4+ T-cells and self-restriction. The interactions between MHCII and peptides determine the specificity of the immune response and are crucial in immunotherapy and cancer vaccine design. With the ever-increasing amount of MHCII-peptide binding data available, many computational approaches have been developed for MHCIIpeptide interaction prediction over the last decade. There is thus an urgent need to provide an up-to-date overview and assessment of these newly developed computational methods. To benchmark the prediction performance of these methods, we constructed an independent dataset containing binding and nonbinding peptides to 20 human MHCII protein allotypes from the Immune Epitope Database, covering DP, DR and DQ alleles. After collecting 11 known predictors up to January 2022, we evaluated those available through a webserver or standalone packages on this independent dataset. The benchmarking results show that MixMHC2pred and NetMHCIIpan-4.1 achieve the best performance among all predictors. In general, newly developed methods perform better than older ones due to the rapid expansion of data on which they are trained and the development of deep learning algorithms. Our manuscript not only draws a full picture of the state-of-art of MHCII-peptide binding prediction, but also guides researchers in the choice among the different predictors. More importantly, it will inspire biomedical researchers in both academia and industry for the future developments in this field. [ABSTRACT FROM AUTHOR]

The AID/APOBECs are a group of zinc-dependent cytidine deaminases that catalyse the deamination of bases in nucleic acids, resulting in a cytidine to uridine transition. Secreted novel AID/APOBEC-like deaminases (SNADs), characterized by the presence of a signal peptide are unique among all of intracellular classical AID/APOBECs, which are the central part of antibody diversity and antiviral defense. To date, there is no available knowledge on SNADs including protein characterization, biochemical characteristics and catalytic activity. We used various in silico approaches to define the phylogeny of SNADs, their common structural features, and their potential structural variations in fish species. Our analysis provides strong evidence of the universal presence of SNAD1 proteins/transcripts in fish, in which expression commences after hatching and is highest in anatomical organs linked to the immune system. Moreover, we searched published fish data and identified previously, "uncharacterized proteins" and transcripts as SNAD1 sequences. Our review into immunological research suggests SNAD1 role in immune response to infection or immunization, and interactions with the intestinal microbiota. We also noted SNAD1 association with temperature acclimation, environmental pollution and sex-based expression differences, with females showing higher level. To validate in silico predictions we performed expression studies of several SNAD1 gene variants in carp, which revealed distinct patterns of responses under different conditions. Dual sensitivity to environmental and pathogenic stress highlights its importance in the fish and potentially enhancing thermotolerance and immune defense. Revealing the biological roles of SNADs represents an exciting new area of research related to the role of DNA and/or RNA editing in fish biology. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex Class II (MHCII) proteins initiate and regulate immune responses by presentation of antigenic peptides to CD4+ T-cells and self-restriction. The interactions between MHCII and peptides determine the specificity of the immune response and are crucial in immunotherapy and cancer vaccine design. With the ever-increasing amount of MHCII-peptide binding data available, many computational approaches have been developed for MHCII-peptide interaction prediction over the last decade. There is thus an urgent need to provide an up-to-date overview and assessment of these newly developed computational methods. To benchmark the prediction performance of these methods, we constructed an independent dataset containing binding and non-binding peptides to 20 human MHCII protein allotypes from the Immune Epitope Database, covering DP, DR and DQ alleles. After collecting 11 known predictors up to January 2022, we evaluated those available through a webserver or standalone packages on this independent dataset. The benchmarking results show that MixMHC2pred and NetMHCIIpan-4.1 achieve the best performance among all predictors. In general, newly developed methods perform better than older ones due to the rapid expansion of data on which they are trained and the development of deep learning algorithms. Our manuscript not only draws a full picture of the state-of-art of MHCII-peptide binding prediction, but also guides researchers in the choice among the different predictors. More importantly, it will inspire biomedical researchers in both academia and industry for the future developments in this field. [ABSTRACT FROM AUTHOR]

A fundamental challenge for personalized medicine is to capture enough of the complexity of an individual patient to determine an optimal way to keep them healthy or restore their health. This will require personalized computational models of sufficient resolution and with enough mechanistic information to provide actionable information to the clinician. Such personalized models are increasingly referred to as medical digital twins. Digital twin technology for health applications is still in its infancy, and extensive research and development is required. This article focuses on several projects in different stages of development that can lead to specific--and practical-medical digital twins or digital twin modeling platforms. It emerged from a two-day forum on problems related to medical digital twins, particularly those involving an immune system component. Open access video recordings of the forum discussions are available. [ABSTRACT FROM AUTHOR]

Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population. The common marmoset (Callithrix jacchus), a Neotropical new-world (platyrrhines) non-human primate, has gained increasing attention as an animal model for a number of diseases given its small size, availability and evolutionary proximity to humans. This review aims to (i) discuss the pros and cons of the common marmoset as an animal model by providing a brief snapshot of how marmosets are currently utilized in biomedical research, (ii) summarize and evaluate relevant aspects of the marmoset immune system to the study of infectious diseases, (iii) provide a historical backdrop, outlining the significance of infectious diseases and the importance of developing reliable animal models to test novel therapeutics, and (iv) provide a summary of infectious diseases for which a marmoset model exists, followed by an in-depth discussion of the marmoset models of two studied bacterial infectious diseases (tularemia and melioidosis) and one viral infectious disease (viral hepatitis C). [ABSTRACT FROM AUTHOR]

Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions. [ABSTRACT FROM AUTHOR]

B cell, clusters of differentiation marker, allergen, cytokine, complement, C-type lectin receptor, immunoglobulin gene, monocytes and dendritic cells. [Extracted from the article]

Background: People living in close quarters, such as military trainees, are at increased risk for skin and soft tissue infections (SSTI), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). The serum immune factors associated with the onset of SSTI are not well understood. Methods: We conducted a longitudinal study of SSTIs, enrolling US Army trainees before starting military training and following up for 14 weeks. Samples were collected on Day 0, 56, and 90. Serum chemokines and cytokines among 16 SSTI cases and 51 healthy controls were evaluated using an electrochemiluminescence based multiplex assay platform. Results: Of 54 tested cytokines, 12 were significantly higher among SSTI cases as compared to controls. Among the cases, there were correlations between factors associated with vascular injury (i.e., VCAM-1, ICAM-1, and Flt1), the angiogenetic factor VEGF, and IL-10. Unsupervised machine learning (Principal Component Analysis) revealed that IL10, IL17A, C-reactive protein, ICAM1, VCAM1, SAA, Flt1, and VGEF were indicative of SSTI. Conclusion: The study demonstrates the power of immunoprofiling for identifying factors predictive of pre-illness state of SSTI thereby identifying early stages of an infection and individuals susceptible to SSTI. [ABSTRACT FROM AUTHOR]

Katalin Karikó and Drew Weissman were given the 2023 Nobel Prize in Physiology or Medicine for their findings of nucleoside base modifications that lead to the development of effective mRNA vaccines against COVID-19. This was a remarkable achievement, given that their initial manuscript was rejected by Nature and Science in 2005. The development of mRNA vaccines lagged for more than a decade for several reasons, including the lack of funding, the perceived risks of the technology, and the scepticism of many scientists. Furthermore, Karikó and Weissman's study appeared to be technical and difficult to understand. The COVID-19 pandemic, on the other hand, has shown the importance of mRNA vaccine technology. COVID-19 mRNA vaccines have been highly effective in preventing serious illness, hospitalization, and death. The Nobel Prize for Karikó and Weissman highlights the importance of perseverance, diversity, and inclusion in translational immunology. We need to build a more inclusive scientific community, where scientists from all backgrounds are supported and their work is valued. This will result in more scientific breakthroughs and better healthcare for everyone. [ABSTRACT FROM AUTHOR]

Diversity of Approaches in Undergrad Teaching The multitude of pedagogic and stylistic approaches for teaching immunology is revealed in articles describing undergraduate immunology classes. Immunology for Students in Healthcare Professions Teaching immunology for the healthcare professions can have some advantages compared to most undergraduate courses. Keywords: immunology; medical; active; learning; education; undergraduate; diversity; laboratory EN immunology medical active learning education undergraduate diversity laboratory 1 3 3 08/04/21 20210802 NES 210802 Introduction This Research Topic addresses issues relevant to teaching of modern immunology, a field that has exploded in recent years and is constantly evolving. [Extracted from the article]

Although anti-C1q autoantibodies have been described more than four decades ago a constant stream of papers describing clinical associations or functional consequences highlights that anti-C1q antibodies are still hot and happening. By far the largest set of studies focus on anti-C1q antibodies is systemic lupus erythematosus (SLE). In SLE anti-C1q antibodies associate with involvement of lupus nephritis in such a way that in the absence of anti-C1q antibodies it is unlikely that a flare in nephritis will occur. Anti-C1q antibodies occur in several autoimmune conditions but also in healthy individuals. Although considerable progress has been made in the understanding of how anti-C1q antibodies may contribute to tissue injury there is still a lot to learn about the processes involved in the breaking of tolerance to this protein. There has been considerable improvement in the assays employed to test for the presence of anti-C1q antibodies. Hopefully with these new and standardized assays at hand larger clinical association studies will be conducted with independent replication. Such large-scale studies will reveal the true value of clinical testing for anti-C1q autoantibodies in several clinical conditions. [ABSTRACT FROM AUTHOR]

This article is an editorial discussing the role of immune cells in type 1 diabetes (T1D) and their impact on the pancreas. The authors highlight the importance of studying immune cells in the pancreas itself, as peripheral measurements may not accurately reflect the conditions in the organ. The editorial also discusses the hyperexpression of HLA-I in T1D pancreas and the potential role of interferons in driving this upregulation. Additionally, the article explores the interplay between peripheral neurons and immune cells in T1D and the potential use of N-glycosylated complement component C3 as a biomarker for T1D progression. The authors emphasize the need for a comprehensive approach to understanding T1D and developing new therapeutics and biomarkers. [Extracted from the article]

The innate immune system not only participates in host defence but also contributes to the control of adaptive immune responses. Complement and Toll-like receptors (TLR) are key components of innate immunity. Emerging evidence suggests their activation is involved in all major aspects of transplantation. This paper reviews the current understanding of how the complement and TLR on impact transplant injury. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb), and its incidence and mortality are increasing. The BCG vaccine was developed in the early 20th century. As the most widely administered vaccine in the world, approximately 100 million newborns are vaccinated with BCG every year, which has saved tens of millions of lives. However, due to differences in region and race, the average protective rate of BCG in preventing tuberculosis in children is still not high in some areas. Moreover, because the immune memory induced by BCG will weaken with the increase of age, it is slightly inferior in preventing adult tuberculosis, and BCG revaccination cannot reduce the incidence of tuberculosis again. Research on themechanism of Mtb and the development of new vaccines against TB are the main strategies for preventing and treating TB. In recent years, Pro-Glumotif-containing (PE) and Pro-Pro-Glu motif-containing (PPE) family proteins have been found to have an increasingly important role in the pathogenesis and chronic protracted infection observed in TB. The development and clinical trials of vaccines based on Mtb antigens are in progress. Herein, we review the immunological effects of PE/PPE proteins and the development of common PE/PPE vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients. Methods: We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients. Results: Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE. Discussion: These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation. [ABSTRACT FROM AUTHOR]

Respiratory infections cause tremendous morbidity and mortality worldwide. Amongst these diseases, tuberculosis (TB), a bacterial illness caused by Mycobacterium tuberculosis which often affects the lung, and coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), stand out as major drivers of epidemics of global concern. Despite their unrelated etiology and distinct pathology, these infections affect the same vital organ and share immunopathogenesis traits and an imperative demand to model the diseases at their various progression stages and localizations. Due to the clinical spectrum and heterogeneity of both diseases experimental infections were pursued in a variety of animal models. We summarize mammalian models employed in TB and COVID-19 experimental investigations, highlighting the diversity of rodent models and species peculiarities for each infection. We discuss the utility of non-human primates for translational research and emphasize on the benefits of non-conventional experimental models such as livestock. We epitomize advances facilitated by animal models with regard to understanding disease pathophysiology and immune responses. Finally, we highlight research areas necessitating optimized models and advocate that research of pulmonary infectious diseases could benefit from cross-fertilization between studies of apparently unrelated diseases, such as TB and COVID-19. [ABSTRACT FROM AUTHOR]

An allergic or type I hypersensitivity reaction involves a misdirected immune overreaction to innocuous environmental and dietary antigens called allergens. The genetic predisposition to allergic disease, referred to as atopy, can be expressed as a variety of manifestations—e.g., allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic asthma, anaphylaxis. Globally, allergic diseases are one the most common types of chronic conditions. Several factors have been identified to contribute to the pathogenesis and progression of the disease, leading to distinctively variable clinical symptoms. The factors which can attenuate or exacerbate allergic reactions can range from genetic heterozygosity, the prominence of various comorbid infections, and other factors such as pollution, climate, and interactions with other organisms and organism-derived products, and the surrounding environment. As a result, the effective prevention and control of allergies remains to be one of the most prominent public health problems. Therefore, to contextualize the current knowledge about allergic reactions, this review paper attempts to synthesize different aspects of an allergic response to describe its significance in the global health scheme. Specifically, the review shall characterize the biomolecular mechanisms of the pathophysiology of the disease based on underlying disease theories and current findings on ecologic interactions and describe prevention and control strategies being utilized. An integrated perspective that considers the underlying genetic, immunologic, and ecologic aspects of the disease would enable the development of more effective and targeted diagnostic tools and therapeutic strategies for the management and control of allergic diseases.

Background: Glucose metabolic reprogramming (GMR) is a cardinal feature of carcinogenesis and metastasis. However, the underlying mechanisms have not been fully elucidated. The aim of this study was to profile the metabolic signature of primary tumor and circulating tumor cells from metastatic colorectal cancer (mCRC) patients using integrated omics analysis. Methods: PET-CT imaging, serum metabolomics, genomics and proteomics data of 325 high 18F-fluorinated deoxyglucose (FDGhigh) mCRC patients were analyzed. The para-tumor, primary tumor and liver metastatic tissues of mCRC patients were used for proteomics analysis. Results: The glucose uptake in tumor tissues as per the PET/CT images was correlated to serum levels of glutamic-pyruvic transaminase (ALT), total bilirubin (TBIL), creatinine (CRE). Proteomics analysis indicated that several differentially expressed proteins were enriched in both GMR and epithelial-mesenchymal transition (EMT)-related pathways. Using a tissue-optimized proteomic workflow, we identified novel proteomic markers (e.g. CCND1, EPCAM, RPS6), a novel PCK1-CDK6-INSR protein axis, and a potential role for FOLR (FR) in GMR/EMT of CRC cells. Finally, CEA/blood glucose (CSR) was defined as a new index, which can be used to jointly diagnose liver metastasis of colorectal cancer. Conclusions: GMR in CRC cells is closely associated with the EMT pathway, and this network is a promising source of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Understanding inflammatory and immune responses to Omicron infection based on age is crucial when addressing this global health threat. However, the lacking of comprehensive elucidation hinders the development of distinct treatments tailored to different age populations. Methods: 1299 cases of Omicron infection in Shanghai were enrolled between April 10, 2022 and June 3, 2022, dividing into three groups by ages: Adult group (18-59 years), Old group (60-79 years), and Elder group (≥ 80 years). Laboratory data including inflammatory cytokines, cellular, and humoral immunity were collected and analyzed. Results: The mean age of Adult, Old, and Elder groups were 44.14, 69.98, and 89.35 years, respectively, with 40.9% being men. The Elder group patients exhibited higher white blood cell (WBC) counts and elevated levels of inflammatory cytokines, but their lymphocyte counts were relatively lower. In comparison to the Old group patients, the Elder group patients demonstrated significantly lower CD3+ T-cell counts, CD3+ T-cell proportion, CD4+ T-cell counts, CD8+ T-cell counts, and CD19+ B-cell counts, while the NK-cell counts were higher. Omicron negative patients displayed a higher proportion of CD19+ B-cells and higher levels of Complement-3 and IL-17 compared to the positive patients in the Old group. Omicron negative patients had lower WBC counts, CD3+ CD8+ T-cells proportion, and the levels of serum amyloid A and IgA in the Elder group, but the CD4+/CD8+ ratio was higher. Conclusions: Our study identified the distinct profiles of inflammatory and immune responses to Omicron infection varying with age and highlighted the diverse correlations between the levels of various biomarkers and Omicron infected/convalescent patients. [ABSTRACT FROM AUTHOR]

Chronic Graft-versus-Host Disease (cGVHD) is a major long-term complication, associated with morbidity and mortality in patients following allogenic hematopoietic cell transplantation (HCT) for immune hematopoietic disorders. The mouth is one of the most frequently affected organs after HCT (45-83%) and oral cGVHD, which may appear as the first visible sign. Manifestations present with mucosal lichenoid lesions, salivary gland dysfunction and limited oral aperture. Diagnosis of oral cGVHD severity is based on mucosal lesions with symptoms of sensitivity and pain and reduced oral intake. However, diagnostic difficulties arise due to subjective definitions and low specificity to cover the spectrum of oral cGVHD. In recent years there have been significant improvements in our understanding of the underlying oral cGVHD disease mechanisms. Drawing upon the current knowledge on the pathophysiology and biological phases of oral cGVHD, we address oral mucosa lichenoid and Sjogren's Syndrome-like sicca syndromes. We consider the response of alloreactive T-cells and macrophages to recipient tissues to drive the pathophysiological reactions and biological phases of acute inflammation (phase 1), chronic inflammation and dysregulated immunity (phase 2), and subsequent aberrant fibrotic healing (phase 3), which in time may be associated with an increased malignant transformation rate. When formulating treatment strategies, the pathophysiological spectrum of cGVHD is patient dependent and not every patient may progress chronologically through the biological stages. As such there remains a need to address and clarify personalized diagnostics and management to improve treatment descriptions. Within this review, we highlight the current state of the art knowledge on oral cGVHD pathophysiology and biological phases. We address knowledge gaps of oral cGVHD, with a view to facilitate clinical management and improve research quality on lichenoid biology and morbid forms of oral cGVHD. [ABSTRACT FROM AUTHOR]

Introduction: Immunity is involved in a variety of bone metabolic processes, especially osteoporosis. The aim of this study is to explore new bone immunerelated markers by bioinformatics method and evaluate their ability to predict osteoporosis. Methods: The mRNA expression profiles were obtained from GSE7158 in Gene expression Omnibus (GEO), and immune-related genes were obtained from ImmPort database (https:/ /www.immport.org/shared/). immune genes related to bone mineral density(BMD) were screened out for differential analysis. protein-protein interaction (PPIs) networks were used to analyze the interrelationships between different immune-related genes (DIRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DIRGs function were performed. A least absolute shrinkage and selection operation (LASSO) regression model and multiple Support Vector Machine-Recursive Feature Elimination (mSVM-RFE) model were constructed to identify the candidate genes for osteoporosis prediction The receiver operator characteristic (ROC) curves were used to validate the performances of predictive models and candidate genes in GEO database (GSE7158,GSE13850). Through the RT - qPCR verify the key genes differentially expressed in peripheral blood mononuclear cells Finally, we constructed a nomogram model for predicting osteoporosis based on five immune-related genes. CIBERSORT algorithm was used to calculate the relative proportion of 22 immune cells. Results: A total of 1158 DEGs and 66 DIRGs were identified between high-BMD and low-BMD women. These DIRGs were mainly enriched in cytokine-mediated signaling pathway, positive regulation of response to external stimulus and the cellular components of genes are mostly localized to external side of plasma membrane. And the KEGG enrichment analysis were mainly involved in Cytokine -cytokine receptor interaction, PI3K-Akt signaling pathway, Neuroactive ligand -receptor interaction,Natural killer cell mediated cytotoxicity. Then five key genes (CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1) were identified and used as features to construct a predictive prognostic model for osteoporosis using the GSE7158 dataset. Conclusion: Immunity plays an important role in the development of osteoporosis.CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1were play an important role in the occurrences and diagnosis of OP. [ABSTRACT FROM AUTHOR]