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In recent years, due to advancements in medical conditions and the development of scientific research, the fundamental research of TCM antitumor treatments has progressed from the cellular level to the molecular and genetic levels. Previous studies have demonstrated the significant role of traditional Chinese medicine (TCM) in antitumor therapy through various mechanisms and pathways. Its mechanism of action is closely associated with cancer biology across different stages. This includes inhibiting tumor cell proliferation, blocking invasion and metastasis to surrounding tissues, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, regulating immune function, maintaining genome stability, preventing mutation, and regulating cell energy metabolism. The use of TCM for eliciting antitumor effects not only has a good therapeutic effect and low side effects, it also provides a solid theoretical basis for clinical treatment and medication. This paper reviews the mechanism of the antitumor effects of TCM based on tumor characteristics. Through our review, we found that TCM not only directly inhibits tumors, but also enhances the body's immunity, thereby indirectly inducing an antitumor effect. This function aligns with the TCM theory of "strengthening the body's resistance to eliminate pathogenic factors". Furthermore, TCM will play a significant role in tumor treatment in clinical settings. [ABSTRACT FROM AUTHOR]

Summary: Since the publication in 2017 of the revised 4th Edition of the World Health Organization (WHO) classification of haematolymphoid tumours, here referred to as WHO‐HAEM4, significant clinicopathological, immunophenotypic and molecular advances have been made in the field of lymphomas, contributing to refining the diagnostic criteria of several diseases, upgrading entities previously defined as provisional and identifying new entities. This process has resulted in two recent classification proposals of lymphoid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, focusing on T‐cell lymphomas and histiocytic/dendritic cell tumours. Moreover, we update the genetic data of the various pathological entities. The main goal is to provide a tool to facilitate the work of the pathologists, haematologists and researchers involved in the diagnosis and treatment of these haematological malignancies. [ABSTRACT FROM AUTHOR]

In this paper, we study a tumor-immune system interaction model with dendritic cell therapy and immune response delay. First, it is shown that the ODE version of the model has a Bogdanov--Takens (BT) singularity or a weak focus with multiplicity at most 1 for different parameter values. As the parameters vary, the ODE model undergoes supercritical Hopf bifurcation and supercritical BT bifurcation. Our analysis indicates that there exists a threshold value of the activation rate of T cells, below which tumor immune escape occurs, above or at which T cells and tumor cells coexist in the form of a stable periodic oscillation or steady state. Second, we study how the immune response delay affects the dynamics of the model. Our results reveal that the delay can destabilize the stable positive equilibrium through Hopf bifurcation. Furthermore, the direction and stability of Hopf bifurcation are derived. When there is a cusp, we show that it is a BT singularity for any delay and the delay model also undergoes BT bifurcation. Finally, numerical simulations are presented to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor- α , and IFN- γ , as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor- β , and tumor necrosis factor- β. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors. [ABSTRACT FROM AUTHOR]

The UVB irradiation is well known for its impact on the development of skin cancer. However, low UVB irradiation plays a protective role against various human diseases including cancer through its effect on tumor suppression. This article summarizes the key findings of the paper by Park et al., which describes a novel molecular mechanism of moderate UVB irradiation in suppressing the growth of melanoma and colorectal cancer. Key observations in this article are that moderate UVB irradiation can enhance tumor immunity by (1) increased infiltration of CD4+ and CD8+ T cells; (2) increased infiltration of CD103+ conventional type 1 dendritic cells (cDC1); and (3) a significant decrease of M2 tumor associate macrophages (TAMs) into the tumor. The authors further identified the role of Batf3 transcription factor in moderate UVB irradiation‐mediated anti‐tumor immune response. Deletion of Batf3 transcription factor reversed the tumor suppressive effect with decreased CD103+ cDC1 cell infiltration. This pre‐clinical study provides a very novel mechanistic insight into the utilization of moderate UVB irradiation for the management of melanoma and colorectal cancer. This study further provides the direction of new future research to explore moderate UVB irradiation in combination with checkpoint blockade antibodies to enhance immunotherapeutic response against various solid tumors. [ABSTRACT FROM AUTHOR]

In this paper, we study a mathematical model of Hepatitis C Virus (HCV) infection. We present a compartmental mathematical model involving healthy hepatocytes, infected hepatocytes, non-activated dendritic cells, activated dendritic cells and cytotoxic T lymphocytes. The derivative used is of non-local fractional order and with non-singular kernel. The existence and uniqueness of the system is proven and its stability is analyzed. Then, by applying the Laplace Adomian decomposition method for the fractional derivative, we present the semi-analytical solution of the model. Finally, some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions. [ABSTRACT FROM AUTHOR]

Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A "cytokine storm", which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer cells, and B cells. So, it has been suggested that the chemokine CXCL10, through CXCR3, is associated with inflammatory diseases and may be involved in the development of COVID-19. Therefore, in this review paper, we focus on the role of CXCL10 overactivity in the pathogenesis of COVID-19. We performed an extensive literature search for our investigation using the MEDLINE/PubMed database. Increased concentrations of CXCL10 were observed in COVID-19. Elevated levels of CXCL10 were reported to be associated with a severe course and disease progression. Published studies revealed that CXCL10 may be a very good predictive biomarker of patient outcome in COVID-19, and that markedly elevated CXCL10 levels are connected with ARDS and neurological complications. It has been observed that an effective treatment for SARS-CoV-2 leads to inhibition of "cytokine storm", as well as reduction of CXCL10 concentrations. It seems that modulation of the CXCL10–CXCR3 axis may be an effective therapeutic target of COVID-19. This review describes the potential role of CXCL10 in the pathogenesis of COVID-19, as well as its potential immune–therapeutic significance. However, future studies should aim to confirm the prognostic, clinical, and therapeutic role of CXCL10 in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV) targets immune cells and tries to inactivate dendritic cells and interferon molecules to continue its replication process. Since EBOV detailed mechanism has not been identified so far, it would be useful to understand the growth and spread of EBOV dynamics based on mathematical methods and simulation approaches. Computational approaches such as Cellular Automata (CA) have the advantage of simplicity over solving complicated differential equations. The spread of Ebola virus in lymph nodes is studied using a simplified Cellular Automata model with only four parameters. In addition to considering healthy and infected cells, this paper also considers T lymphocytes as well as cell movement ability during the simulation in order to investigate different scenarios in the dynamics of an EBOV system. It is shown that the value of the probability of death of T cells affects the number of infected cells significantly in the steady-state. For a special case of parameters set, the system shows oscillating dynamics. The results were in good agreement with an ordinary differential equation-based model which indicated CA method in combination with experimental discoveries could help biologists find out more about the EBOV mechanism and hopefully to control the disease. [ABSTRACT FROM AUTHOR]

In a recent paper, Schriek et al. show that, in a complement-dependent reaction, marginal zone B cells (MZBs) steal MHC class II (MHCII) from dendritic cells (DCs). Activation of T cells by stolen MHCII complexes potentially allows MZBs to augment or regulate T cell activation in ways that are distinct from DCs. [ABSTRACT FROM AUTHOR]

Immunotherapy is considered as an effective method for cancer treatment owing to the induction of specific and long-lasting anti-cancer effects. Immunotherapeutic strategies have shown significant success in human malignancies, particularly in prostate cancer (PCa), a major global health issue regarding its high metastatic rates. In fact, the first cancer vaccine approved by FDA was Provenge, which has been successfully used for treatment of PCa. Despite the remarkable success of cancer immunotherapy in PCa, many of the developed immunotherapy methods show poor therapeutic outcomes. Immunosuppression in tumor microenvironment (TME) induced by non-functional T cells (CD4+ and CD8+), tolerogenic dendritic cells (DCs), and regulatory T cells, has been reported to be the main obstacle to the effectiveness of anti-tumor immune responses induced by an immunotherapy method. The present review particularly focuses on the latest findings of the immune checkpoints (ICPs), including CTLA-4, PD-1, PD-L1, LAG-3, OX40, B7-H3, 4-1BB, VISTA, TIM-3, and ICOS; these checkpoints are able to have immune modulatory effects on the TME of PCa. This paper further discusses different approaches in ICPs targeting therapy and summarizes the latest advances in the clinical application of ICP-targeted therapy as monotherapy or in combination with other cancer therapy modalities in PCa. [ABSTRACT FROM AUTHOR]

Aim: The objective of this review is to describe the immunological mechanisms which facilitate maternal tolerance at the maternal‐placental interface, and to discuss how these mechanisms are disrupted in pre‐eclampsia. Methods: A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the immunological mechanisms which facilitate maternal tolerance in healthy pregnancy and pre‐eclampsia are presented in this article. Results: The maternal‐placental interface is the site where the immune tolerance begins and develops. Within the innate immunity, natural killer cells, macrophages and dendritic cells play a pivotal role in tolerance through regulation of inflammation. On the other hand, within the adaptive immunity, the correct increase of regulatory T cells is crucial for ensuring immune tolerance toward placental cells. Disturbances in maternal tolerance can lead to the appearance of pregnancy complications such as pre‐eclampsia, which has a considerable impact on perinatal morbidity and mortality. Conclusion: Our partial knowledge of immunological mechanisms involved in tolerance at the maternal‐placental interface indicates that pre‐eclampsia is characterized by alterations of this maternal immune tolerance, which could represent the origin of the disease. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is the major cause of seasonal epidemics and flu outbreaks worldwide. Given that interleukin 16 (IL16) can regulate T cell function and is one of the signature markers for virus infection including IAV infection, the impact of IL16 on IAVinduced T cell immune response hasn't been elucidated yet. In this paper, we infected wild type and IL16 knockout (KO) mice with IAV and analyzed the immunity of mice by flow cytometry. We observed an increase in the percentage of T helper (Th) 1 cells in the spleens of IL16 KO mice and elevation of IFN-α and TNF-α secretion from CD8+ T cells in the lungs and spleens of IL16 KO mice in response to IAV infection. Moreover, the expression of major histocompatibility complex II which represents the maturation of dendritic cells (DCs) was upregulated in the lungs of IL16 KO mice. Taken together, our study suggests that IL16 deficiency enhanced Th1 and cytotoxic T lymphocyte response as well as DC maturation upon IAV infection, which provides new insight into the host regulation of T cell immune responses during IAV infection. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the most effective professional antigen-presenting cell. They ferry antigen from the extremities to T cells and are essential for the initiation of an adaptive immune response. Despite interest in how DCs respond to chemical stimuli, there have been few attempts to model DC migration. In this paper, we simulate the motility of DCs by modeling the generation of forces by filopodia and a force balance on the cell. The direction of fliopodial extension is coupled to differential occupancy of cognate chemokine receptors across the cell. Our model simulates chemokinesis and chemotaxis in a variety of chemical and mechanical environments. Simulated DCs undergoing chemokinesis were measured to have a speed of 5.1 ± 0.07 μm·min-1 and a persistence time of 3.2 ± 0.46 min, consistent with experiment. Cells undergoing chemotaxis exhibited a stronger chemotactic response when exposed to lower average chemokine concentrations, also consistent with experiment. We predicted that when placed in two opposing gradients, cells will cluster in a line, which we call the “line of equistimulation;” this clustering has also been observed. We calculated the effect of varying gradient steepness on the line of equistimulation, with steeper gradients resulting in tighter clustering. Moreover, gradients are found to be most potent when cells are in a gradient of chemokine whose mean concentration is close to the binding of the Kd to the receptor, and least potent when the mean concentration is 0.1Kd. Comparing our simulations to experiment, we can give a quantitative measure of the strength of certain chemokines relative to others. Assigning the signal of CCL19 binding CCR7 a baseline strength of 1, we found CCL21 binding CCR7 had a strength of 0.28, and CXCL12 binding CXCR4 had a strength of 0.30. These differences emerge despite both chemokines having virtually the same Kd, suggesting a mechanism of signal amplification in DCs requiring further study. [ABSTRACT FROM AUTHOR]

Many mRNA-based vaccines have been investigated for their specific potential to activate dendritic cells (DCs), the highly-specialized antigen-presenting cells of the immune system that play a key role in inducing effective CD4+ and CD8+ T-cell responses. In this paper we report a new vaccine/gene delivery platform that demonstrates the benefits of using a self-amplifying (“replicon”) mRNA that is protected in a viral-protein capsid. Purified capsid protein from the plant virus Cowpea Chlorotic Mottle Virus (CCMV) is used to in vitro assemble monodisperse virus-like particles (VLPs) containing reporter proteins (e.g., Luciferase or eYFP) or the tandem-repeat model antigen SIINFEKL in RNA gene form, coupled to the RNA-dependent RNA polymerase from the Nodamura insect virus. Incubation of immature DCs with these VLPs results in increased activation of maturation markers – CD80, CD86 and MHC-II – and enhanced RNA replication levels, relative to incubation with unpackaged replicon mRNA. Higher RNA uptake/replication and enhanced DC activation were detected in a dose-dependent manner when the CCMV-VLPs were pre-incubated with anti-CCMV antibodies. In all experiments the expression of maturation markers correlates with the RNA levels of the DCs. Overall, these studies demonstrate that: VLP protection enhances mRNA uptake by DCs; coupling replicons to the gene of interest increases RNA and protein levels in the cell; and the presence of anti-VLP antibodies enhances mRNA levels and activation of DCs in vitro. Finally, preliminary in vivo experiments involving mouse vaccinations with SIINFEKL-replicon VLPs indicate a small but significant increase in antigen-specific T cells that are doubly positive for IFN and TFN induction. [ABSTRACT FROM AUTHOR]

The article introduces scientific conference papers on T cells and skin to be presented at the 22nd Scientific meeting 2014 of the Fondation René Touraine (FRT), a European non-governmental organization that promotes therapeutic progress in dermatology, on 5th December 2014 in Paris, France. Papers by researchers Shimon Sakaguchi, Federica Sallusto and Thomas Gebhardt are included. Specific topics include immune abnormalities found in atopic dermatitis and adoptive transfer of dendritic cells.

Oncolytic virus (OV) is a replication competent virus that selectively invades cancer cells; as these cells die under the viral burden, the released virus particles proceed to infect other cancer cells. Oncolytic viruses are designed to also be able to stimulate the anticancer immune response. Thus, one may represent an OV by two parameters: its replication potential and its immunogenicity. In this paper we consider a combination therapy with OV and a checkpoint inhibitor, anti-PD-1. We evaluate the efficacy of the combination therapy in terms of the tumor volume at some later time, for example, 6 months from initial treatment. Since T cells kill not only virus-free cancer cells but also virus-infected cancer cells, the following question arises: Does increasing the amount of the checkpoint inhibitor always improve the efficacy? We address this question, by a mathematical model consisting of a system of partial differential equations. We use the model to construct, by simulations, an efficacy map in terms of the doses of the checkpoint inhibitor and the OV injection. We show that there are regions in the map where an increase in the checkpoint inhibitor actually decreases the efficacy of the treatment. We also construct efficacy maps with checkpoint inhibitor vs. the replication potential of the virus that show the same antagonism, namely, an increase in the checkpoint inhibitor may actually decrease the efficacy. These results have implications for clinical trials. [ABSTRACT FROM AUTHOR]

Cross-presentation of apoptotic cell associated antigens by immature dendritic cells prevents the activation of self reactive CD8 T cells. Tolerized self reactive CD8 T cells down-regulate IL-7R expression on their surface. Whether over-expression of IL-7R can reverse their fate and function has not been examined. In this paper, we showed forced expression of IL-7R in OT-I T cells by a transgene enhanced CD8 T cell mediated diabetes in the RIP-mOVA model. Although IL-7R Tg (transgenic) did not completely reverse the deletion of OT-I T cells, it provided a significant survival advantage over w.t OT-I T cells. Furthermore, IL7R Tg OT-I T cells isolated from diabetic pancreata displayed increased production of IFN-γ, higher expression of T-bet, and increased externalization of CD107a. We also found that immature DCs containing apoptotic cells expressed high levels of PDL-1 on their surface. Although IL-7R Tg did not change PD1 expression on activated OT-I cells in vivo, the transgene enabled a significantly lower number of OT-I T cells to induce diabetes in the absence of PDL-1. Our results demonstrated that forced expression of IL-7R not only improved the functionality of tolerized CD8 T cells, it also acted in synergy with PDL-1 deficiency to further promote CD8 T cell cytotoxicity to self antigens. [ABSTRACT FROM AUTHOR]

T-cells and antigen presenting cells are an essential part of the adaptive immune response system and how they interact is crucial in how the body effectively fights infection or responds to vaccines. Much of the experimental work studying interaction forces between cells has looked at the average properties of bulk samples of cells or applied microscopy to image the dynamic contact between these cells. In this paper we present a novel optical trapping technique for interrogating the force of this interaction and measuring relative interaction forces at the single-cell level. A triple-spot optical trap is used to directly manipulate the cells of interest without introducing foreign bodies such as beads to the system. The optical trap is used to directly control the initiation of cell-cell contact and, subsequently to terminate the interaction at a defined time point. The laser beam power required to separate immune cell pairs is determined and correlates with the force applied by the optical trap. As proof of concept, the antigen-specific increase in interaction force between a dendritic cell and a specific T-cell is demonstrated. Furthermore, it is demonstrated that this interaction force is completely abrogated when T-cell signalling is blocked. As a result the potential of using optical trapping to interrogate cellular interactions at the single cell level without the need to introduce foreign bodies such as beads is clearly demonstrated. [ABSTRACT FROM AUTHOR]

Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]

In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at ‘roughly’ twice the dosage level; if that is the case, then we say that there is a positive ‘synergy’ for this combination of dosages. To address this question, we develop a mathematical model using a system of partial differential equations. The variables include dendritic and cancer cells, CD4+ and CD8+ T cells, IL-12 and IL-2, GM-CSF produced by the vaccine, and a T cell checkpoint inhibitor associated with PD-1. We use the model to explore the efficacy of the two drugs, separately and in combination, and compare the simulations with data from mouse experiments. We next introduce the concept of synergy between the drugs and develop a synergy map which suggests in what proportion to administer the drugs in order to achieve the maximum reduction of tumor volume under the constraint of maximum tolerated dose. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity (DTH) reaction induced by repeated contact with sensitizers. The ability of a chemical to act as a sensitizer has most frequently been tested in animals. As the use of animals for these purposes is gradually and globally being phased out, there is a need for reliable in vitro surrogate assays. Currently proposed in vitro assays are designed to test four key events of the adverse outcome pathway (AOP) involving covalent modification of self-proteins by sensitizers (haptenation) and presentation of new antigens (hapten/carrier complexes) to the immune system. There appears to be imperfect alignment of in vitro assays with clinical and/or animal data, suggesting possibly additional mechanisms of ACD development. Indeed, studies on allergies to small drugs, small chemical-induced HLA-peptide exchange for vaccination purposes and cosmetic ingredient-induced exposure of autoantigens suggest a possibility of DTH response promotion by hapten/carrier-independent mechanisms. Therefore, there is a need for additional appropriate in vitro assays, in order to achieve maximal concordance between clinical and/or animal data and in vitro assays. In this paper, we will review evidence supporting the idea of diverse mechanisms of ACD development. We will also discuss the impact of these multiple mechanisms, on the AOP and on the in vitro assays that should be used for allergen detection. We will propose alloreactivity-like reactions, aided by computer modeling and biochemical tests of compound-HLA binding, as additional tools for better prediction of DTH reactions, resulting from exposure to ingredients in cosmetic products. The combination of the proposed tests, along with the existing assays, should further enhance animal-free assessment of sensitizing potential of individual chemicals. [ABSTRACT FROM AUTHOR]

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named “L-DC” since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

While the cytoskeletal protein talin binds to the β-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the α-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1−/− T-cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1 − / − T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1 − / − T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. Whether direct cell-cell interactions are important in modulating MC/DC function is unclear . In this paper, we show that direct contact between MCs and DCs occurs and plays an important role in modulating the immune response. Activation of MCs through FceRI cross-linking triggers the formation of stable cell-cell interactions with immature DCs that are reminiscent of the immunological synapse. Direct cellular contact differentially regulates the secreted cytokine profile, indicating that MC modulation of DC populations is influenced by the nature of their interaction. Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. The transferred material is ultimately processed and presented by DCs and can activate T cells. The physiological outcomes of the MC-DC synapse suggest a new role for intercellular crosstalk in defining the immune response. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Traditional Chinese herbal medicine (CHM) has a long-history for treatment of various human diseases including tumors, infection, autoimmune diseases in Asian countries, especially in China, Japan, Korea and India. CHM was traditionally used as water extracts and many Chinese herbs were considered to be good for health, which can regulate immune system to protect host from diseases. With the progress of technology, the components of CHM were identified and purified, which included polysaccharides, saponins, phenolic compounds, flavonoids and so on. Recently, accumulating evidence indicates that CHM and its components can regulate immune system through targeting dendritic cells (DCs). We hereby reviewed the immunoregulatory effects of CHM on the maturation, cytokine production and function of DCs. This should help to shed light on the potential mechanism of CHM to improve the usage and clinical efficacy of CHM. Materials and methods Literatures about the effects of CHM on DCs were searched in electronic databases such as Pubmed, Google Scholar and Scopus from 2000 to 2014. ‘CHM’, ‘DC’ or ‘immune’ were used as keywords for the searches. We only reviewed literatures published in English. Results Over 600 publications were found about ‘CHM&immune’ and around 120 literatures about ‘CHM&DC’ were selected and reviewed in this paper. All publications are backed by preclinical or clinical evidences both in vitro and in vivo . Some CHM and its components promote the maturation, pro-inflammatory cytokine production and function of DCs and as the adjuvant enhance immune responses against tumor and infection. In contrast, other CHM and its components suppress the activation status of DCs to induce regulatory T cells, inhibit allergic and inflammatory responses, ameliorate autoimmune diseases, and prolong the allograft survival. A large body of evidence shows that CHM and its components regulate the activation status of DCs through TLRs, NF-κB, MAPK signaling pathways. Conclusion This review provides useful information for understanding the mechanism of CHM on the treatment of diseases, which facilitates to improve the efficacy of CHM. Based on the immunoregulatory effects of CHM on DCs, it indicated that some CHM and its components could be use to develop adjuvant to enhance antigen-specific immune responses or tolerogenic adjuvant to generate antigen-specific immune tolerance. [ABSTRACT FROM AUTHOR]

Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes that require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play a pivotal role in initiating antigen-specific tumor immunity. However, the abnormal function of DCs owing to the immunosuppressive tumor microenvironment (TME) and the insufficient number of tumor infiltrating DCs could promote immune tolerance and tumor immune escape. Thus, there is great potential to employ DCs to induce efficient antitumor immunity. In this paper, we developed intelligent DCs (iDCs), which consist of nanoparticles loaded with photothermal agents (IR-797) and coated with a mature DC membrane. The DC cell membrane on the surface of iDCs preserves the ability to present antigens and prime T cells. The iDCs can also enter the lymph node and stimulate T cells. The activated T cells reduced the expression of heat shock proteins (HSPs) in tumor cells, rendering them more sensitive to heat stress. Subsequently, we used mild photothermal therapy (42–45 °C) to induce immunogenic cell death and contribute to a synergistic antitumor effect. iDCs as a refined and precise system in combination with DC-based immunotherapy and thermal therapy can be stored long-term and on a large scale, so they can be applied in many patients. [ABSTRACT FROM AUTHOR]

Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most common inflammatory skin disease, affecting an average of 2–4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease. [ABSTRACT FROM AUTHOR]

Cortical F-actin plays important roles during HIV-1 infection. A recent paper in Cell highlights the involvement of F-actin in enhancing dendritic cell (DC)-mediated HIV-1 infection of T cells. Such a critical mechanism of HIV-1 trans -enhancement between human DCs and T cells had not been analyzed in molecular detail before this work. [ABSTRACT FROM AUTHOR]

Chronic inflammation of the adipose tissue (AT) is a critical component of obesity-induced insulin resistance and type 2 diabetes. Adipose tissue immune cells, including AT macrophages (ATMs), AT dendritic cells (ATDCs), and T cells, are dynamically regulated by obesity and participate in obesity-induced inflammation. Among AT resident immune cells, ATDCs are master immune regulators and engage in crosstalk with various immune cells to initiate and regulate immune responses. However, due to confounding markers and lack of animal models, their exact role and contribution to the initiation and maintenance of AT inflammation and insulin resistance have not been clearly elucidated. This paper reviews the current understanding of ATDCs and their role in obesity-induced AT inflammation. We also provide the potential mechanisms by which ATDCs regulate AT inflammation and insulin resistance in obesity. Finally, this review offers perspectives on ways to better dissect the distinct functions and contributions of ATDCs to obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma is the most common primary bone tumor and has a poor prognosis. Therefore, it is important to understand the mechanism of the development of osteosarcoma to overcome therapy resistance. Several mathematical models have been developed to study the initiation and progression of many cancer types. However, there are currently no mathematical models for the progression of osteosarcoma, to the best of our knowledge. In this work, we develop a data-driven mathematical model to analyze the impact of the immune cell interactions on the growth of osteosarcoma tumors that have distinct immune patterns. Our model provides a foundation for investigating the effect of various treatments on the dynamics of key players in the primary tumor, including immune cells and cytokines, and ultimately the whole tumor. As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance of immune cells as estimated from their gene expression profiles. We then analyze the tumor progression and effects of the immune system on cancer growth in each cluster. Cluster 3, which had approximately the same number of naive and M2 macrophages, had the slowest tumor growth, and cluster 2, with the highest population of naive macrophages, had the highest cancer population at the steady states. We also found that the fastest growth of cancer occurred when the anti-tumor immune cells and cytokines, including dendritic cells, helper T cells, cytotoxic cells, and IFN- γ , switched from increasing to decreasing, while the dynamics of regulatory T cells switched from decreasing to increasing. Importantly, the most impactful immune parameters on the number of cancer and total cells were the activation and decay rates of the macrophages and regulatory T cells for all clusters. This work presents the first osteosarcoma progression model, which can be later extended to investigate the effectiveness of various osteosarcoma treatments. [ABSTRACT FROM AUTHOR]

The mechanisms through which tumor antigen-specific T cells are elicited in natural or chemotherapy-induced immunosurveillance have been elusive. In this issue of Cancer Cell , two papers by Broz and colleagues and Ruffell and colleagues delineate an important role for a specific dendritic cell subset characterized by CD103 expression, dependence on transcription factors Batf3 and Irf8, and interleukin-12 production. [ABSTRACT FROM AUTHOR]