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T helper type 9 (Th9) cells play important roles in immune responses by producing interleukin‐9 (IL‐9). Several transcription factors are responsible for Th9 cell differentiation; however, transcriptional regulation of Th9 cells is not fully understood. Here, it is shown that Id1 is an essential transcriptional regulator of Th9 cell differentiation. Id1 is induced by IL‐4 and TGF‐β. Id1‐deficient naïve CD4 T cells fail to differentiate into Th9 cells, and overexpression of Id1 induce expression of IL‐9. Mass spectrometry analysis reveals that Id1 interacts with Tcf3 and Tcf4 in Th9 cells. In addition, RNA‐sequencing, chromatin immunoprecipitation, and transient reporter assay reveal that Tcf3 and Tcf4 bind to the promoter region of the Il9 gene to suppress its expression, and that Id1 inhibits their function, leading to Th9 differentiation. Finally, Id1‐deficient Th9 cells ameliorate airway inflammation in an animal model of asthma. Thus, Id1 is a transcription factor that plays an essential role in Th9 cell differentiation by inhibiting Tcf3 and Tcf4. [ABSTRACT FROM AUTHOR]

Iodine excess may cause and aggravate autoimmune thyroiditis (AIT), which is regarded as a typical kind of autoimmune disease mainly mediated by CD4+ T cells. Thus far, it is unclear whether T helper (Th) 9 cells, a novel subpopulation of CD4+ T cells, play a potential role in AIT. Therefore, in the present study, changes in Th9 cells were detected in murine models of AIT induced by excess iodine intake to explore the possible immune mechanism. Female C57BL/6 mice were divided into 7 groups (n = 8) and were supplied with water containing 0.005% sodium iodide for 0, 2, 4, 6, 8, 10, and 12 weeks. With the extension of the high-iodine intake duration, the incidence of thyroiditis and the spleen index were significantly increased, and serum thyroglobulin antibody (TgAb) titers and interleukin 9 (IL-9, major cytokine from Th9 cells) concentrations were also increased. Additionally, it was revealed that the percentages of Th9 cells in spleen mononuclear cells (SMCs) and thyroid tissues were both markedly elevated and accompanied by increased mRNA and protein expression of IL-9 and key transcription factors of Th9 cells (PU.1 and IRF-4). Significantly, dynamic changes in Th9 cells were found, with a peak at 8 weeks after high iodine intake, the time point when thyroiditis was the most serious. Importantly, Th9 cells were detected in the areas of infiltrating lymphocytes in thyroid sections. In conclusion, the continuously increasing proportions of Th9 cells may play an important role in the occurrence and development of AIT induced by high iodine intake. [ABSTRACT FROM AUTHOR]

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+ T cells, which led to improved antitumor outcomes. Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation. Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

• miR-143/145 expression decreases gradually during the differentiation process of Th9 cells. • miR-143/145 inhibits Th9 cell differentiation. • NFATc1 is a direct common target of miR-143/145 in T cells. • Downregulation of NFATc1 inhibits Th9 cell differentiation. • Overexpression of NFATc1 reversed inhibitory effects of miR-143/145 on Th9 cell. Th9 cells are a defined CD4+ helper T cell subgroup found to promote or suppress oncogenesis in a context-dependent manner. How microRNAs (miRNAs) shape Th9 cell functionality, however, remains to be studied. Herein, we determined that miR-143/145 is downregulated during Th9 differentiation. When these miRNAs were upregulated, this inhibited Th9 differentiation, proliferation, and IL-9 production. Overexpressing miR-143/145 in Th9 cells further suppressed NFATc1 expression at the protein and mRNA level, whereas the opposite phenotype was observed when miR-143/145 was downregulated in these cells. NFATc1 silencing markedly inhibited Th9 cell differentiation, whereas overexpressing this transcription factor was sufficient to reverse miR-143/145-associated phenotypes in these cells. These findings thus indicate that the ability of miR-143/145 to inhibit Th9 cell differentiation is attributable to their ability to target and suppress NFATc1 expression. Overall, our results highlight a novel mode of action whereby miR-143/145 controls Th9 differentiation, suggesting that this pathway may be amenable to therapeutic targeting in the context of anti-cancer treatment in the future. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is characterized by intense infiltration of IgG4-positive plasma cells in affected organs. However, the mechanisms acting in the immune responses in IgG4-RD are not fully understood. The aim of this study was to dissect the mechanism underlying the immunoglobulin class switch in IgG4-RD by addressing the crosstalk between IL-35-producing and Th9 cells. The expression level of IL-35 was examined in plasma samples from patients with hepatobiliary and/or pancreatic manifestations of IgG4-RD. Our data demonstrate that IgG4-RD patients exhibit significantly high-level productions of IL-35 as compared to disease and healthy controls. We detected the two subunits of IL-35, EBI3 and IL-12p35, in the two major affected organs, liver and pancreatic tissue, from IgG4-RD. The EBI3- and IL-12p35-positive cells were significantly higher in affected organs in IgG4-RD as compared to disease controls. The colocalization of EBI3 with CD19 and CD38, markers for B cells, suggest the presence of IL-35-producing B cells in affected organs in IgG4-RD. The effects of IL-35 in Th9 differentiation and IL-9 in production of immunoglobulin were then assessed. Surprisingly, IL-35 treatment promoted naïve CD4 T cell differentiating towards Th9 cells through IRF4 signaling. As a consequence, IL-9 secreted by Th9 cells promoted the differentiation of plasma cells and production of IgG1 and IgG4, predominantly IgG4. In conclusion, our data demonstrate that IL-35 actively participates in the process of inflammation and plays an important role in Th9 differentiation resulting in an immunoglobulin class switch towards IgG4. [ABSTRACT FROM AUTHOR]

Abstract Background Interleukin-9 (IL-9) was reported as an active participant in the pathogenesis of allergic asthma. This study aimed to investigate the major source ofIL-9 and its effect on interferon γ (IFN-γ) and immunoglobulin (Ig) secretion by B cells. Methods We isolated peripheral blood mononuclear cells from children with allergic asthma and healthy children. IL-9, IL-4 and IFN-γ expression were detected by ELISA, ELISpot and Flowcytometry. Expression of transcription factor PU.1 was measured by Western Blot. We evaluated the effect of IL-9 on B cell activation and Ig production. Results Results showed that compared with healthy children, levels of IL-9, IL-4 and PU.1 were elevated and levels of IFN-γ were lower in children with allergic asthma. IL-9-expressing CD4+ T cells did not co-express IL-4. Exogenous IL-9 inhibited IFN-γ production in a dose-dependent manner. Antigen-specific Th9 cells existed in children with house dust mite allergic asthma. IL-9 up-regulated expression of CD69 and CD25 on B cells and combination of IL-9 and IL-4 enhanced IgE production. Conclusions In conclusion, our results showed that Th9 cells may be the major source of IL-9 in children with allergic asthma. In these patients, IL-9 impairs IFN-γ production and synergistically promotes IL-4-induced IgE secretion.

Abstract Background Th1, Th2, Th17, Treg and Tfh cells play important roles in schistosomiasis. Th9 cells secrete IL-9 as a signature cytokine and contribute to several classes of inflammatory disease. However, the effects of Th9 cells in schistosomiasis are unknown. We aimed to explore the dynamic changes and potential roles of Th9 cells in the pathogenesis of hepatic egg granulomatous inflammation in mice infected with Schistosoma japonicum. Methods Twenty mice with S. japonicum infection and five normal controls (NC) were used as models. The average areas of egg granulomas were estimated by hematoxylin-eosin (H & E) staining. Hepatic IL-9 and transcription factor PU.1 levels were detected by immunohistochemistry. Flow cytometry techniques were used to analyze the proportions of Th9 cells. With the help of ELISA, serum levels of IL-9 were examined. Results The egg granulomas began to form from four weeks after infection and continued to develop. In parallel with the development of egg granulomas, the hepatic levels of IL-9 and PU.1 increased very slowly during the first four weeks post-infection and increased rapidly thereafter. Moreover, the proportions of splenic Th9 cells and levels of serum IL-9 had similar developmental trends with the egg granulomas. Conclusion The proliferation of Th9 cells and levels of IL-9 were significantly higher in S. japonicum-infected mice compared to NC. In addition, dynamic changes of Th9 and IL-9 were synchronous with the developmental trend of hepatic egg granulomatous inflammation, suggesting that Th9 cells might be a new subset in the pathogenesis of schistosomiasis.

The helper T cell 9 (Thelper-9, Th9), as a functional subgroup of CD4+T cells, was first discovered in 2008. Th9 cells expressed transcription factor PU.1 and cytokine interleukin-9 (IL-9) characteristically. Recent researches have shown that the differentiation of Th9 cells was coregulated by cytokine transforming growth factor β, IL-4, and various transcription factors. Th9 cells, as a new player, played an important role in various immune-related diseases, including tumors, inflammatory diseases, parasite infection, and other diseases. In this article, we summarize the related research progress and discuss the possible prospect. [ABSTRACT FROM AUTHOR]

• Mangiferin exhibits anti-asthma activity. • Functional role of anti-asthma in attenuating EOS and goblet cells infiltration. • Mangiferin regulates Th9, Th17 and Treg cells responses. Mangiferin is the major bioactive ingredient in the leaves of Mangifera indica L., Aqueous extract of such leaves have been traditionally used as an indigenous remedy for respiratory diseases including cough and asthma in Traditional Chinese Medicine. Mangiferin was shown to exert its anti-asthmatic effect by modulating Th1/Th2 cytokines imbalance via STAT6 signaling pathway. However, compelling evidence indicated that subtypes of T helpers and regulatory T cells other than Th1/Th2 were also involved in the pathogenesis of asthma. In current study, we investigated the effects of mangiferin on the differentiation and function of Th9, Th17 and Treg cells in a chicken egg ovalbumin (OVA)-induced asthmatic mouse model. Mangiferin significantly attenuated the symptoms of asthma attacks, reduced the total number of leukocytes, EOS and goblet cells infiltration in lung. Simultaneously, treatment with mangiferin remarkably decreased the proportion of Th9 and Th17 cells; reduced the levels of IL-9, IL-17A; inhibited the expression of PU.1 and RORγt in lung. However, the proportion of Treg cells, the expression of IL-10, TGF-β1 and Foxp3 were increased by mangiferin. Our data suggest that mangiferin exerted anti-asthmatic effect through decreasing Th9 and Th17 responses and increasing Treg response in OVA-induced asthmatic mouse model. [ABSTRACT FROM AUTHOR]

T H 9 cells have emerged as important mediators of allergic airway inflammation. There is evidence that general control nonderepressible 2 (GCN2) affects the immune response under some stress conditions. However, whether GCN2 regulates CD4+ T-cell differentiation during allergic inflammation remains unknown. We sought to clarify the regulatory roles of GCN2 in CD4+ T-cell subset differentiation and its significance in patients with allergic airway inflammation. The effects of GCN2 in differentiation of T H cell subsets were detected by using the in vitro induction system. GCN2 knockout mice, ovalbumin-induced allergic airway inflammation, and adoptive transfer mouse models were used to determine the significance of GCN2 in T H 9 differentiation and allergic airway inflammation in vivo. RNA sequencing, real-time PCR, Western blotting, and other molecular approaches were used to identify the molecular mechanisms relevant to regulation of GCN2 in T H 9 cell differentiation. GCN2 deficiency significantly inhibited differentiation of T H 9 cells but not T H 1, T H 2, and regulatory T cells. GCN2 knockout mice and recombination-activating gene 2 knockout (Rag2KO) mice that received adoptively transferred GCN2-deficient CD4+ T cells exhibited reduced T H 9 differentiation and less severe allergic airway inflammation. Furthermore, the isolated GCN2-deficient T H 9 cells also mediated less severe allergic airway inflammation on adoptive transfer. Mechanistically, GCN2 deficiency inhibits T H 9 cell differentiation through a hypoxia-inducible factor 1α–dependent glycolytic pathway. Our results reveal a novel role of GCN2 in T H 9 cell differentiation. Our findings indicate that new strategies to inhibit GCN2 activity might provide novel approaches to attenuate allergic airway inflammation. [ABSTRACT FROM AUTHOR]

The newly discovered Th9 cells are the distinct subset of CD4+ T helper (Th) cells, which are involved in various pathophysiological conditions of an immune response. In addition to its role in allergic inflammation and elimination of extracellular pathogens, Th9 cells were found to play a key role in inducing anti-tumor immune response. Precisely, the anti-tumor functions of Th9 cells were found to be superior as compared to Th1 and other Th subsets. Th9 cells eliminate tumors via activating innate and adaptive immune cells, and in particular, generating a profound effector cytotoxic T lymphocyte (CTL) response against neo antigens. In addition, it was proposed that Th9 cells were found to induce effector functions of innate cells like dendritic cells, mast cells and NK cells, which further promote a robust anti-tumor immune response. In this review, we highlight the recent advances in differentiation and functions of Th9 cells in anti-tumor immunity. [ABSTRACT FROM AUTHOR]

Breast cancer is a major cause of cancer-related death in women. Antitumor T cell responses play critical therapeutic roles, including direct cytotoxicity mediated by CD8 + T cells and immunomodulatory roles mediated by CD4 + T cells. The IL-9-expressing Th9 cells are recently found to present antitumor immunity in melanoma and lung adenocarcinoma. In this study, we found that IL-9 expression in the serum and in circulating CD4 + T cells were significantly upregulated in breast cancer patients compared to healthy controls. The IL-9-expressing Th9 cells were enriched in the CCR4 − CCR6 − CXCR3 − subset. Upon TCR stimulation, this subset also presented potent IL-10 and IL-21 expression in addition to IL-9 expression. CCR4 − CCR6 − CXCR3 − CD4 + T cells also assisted in the killing of autologous tumor cells by CD8 + T cells, but did not initiate cytotoxicity by themselves. This enhancement in CD8 + T cell-mediated cytotoxicity was dependent on IL-9 as well as on IL-21. Interestingly, the tumor-infiltrating Th9 cells presented comparable IL-9, reduced IL-10, and elevated IL-21 expression compared with their counterparts in the peripheral blood. Together, these results demonstrated that IL-9-expressing Th9 cells were upregulated in breast cancer patients and potentially possessed antitumor roles by enhancing CD8 + T cell-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Takayasu's arteritis (TAK) is a type of large vessel vasculitis which involves the aorta and its major branches. Interleukin (IL)-9 or IL-9-producing Th9 cells were found to be involved in pathogenesis of autoimmune arteritis such as giant cell arteritis, but IL-9 or Th9 cells in TAK were not well known. Here, this study aims to analyze the levels of serum IL-9 and their major source Th9 cells in TAK. With the help of cytometric bead array (CBA), a total of 21 patients with TAK were examined for serum levels of cytokines IL-4, IL-6, IL-8, IL-17, IL-10, TNF-α, IFN-γ, and IL-9. Flow cytometry techniques were used to examine the frequencies of Th9 cells from peripheral blood mononuclear cells (PBMCs) for 11 patients with active TAK and 10 healthy controls. Higher serum levels of serum IL-6 ( P < 0.05), TNF-α ( P < 0.05), and IL-9 level ( P < 0.05) were observed in TAK patients compared to those of healthy controls. Higher frequencies of CD4 IL-9 T cells and CD4 PU.1 T cells in PBMCs and IL-9 PU.1 T cells in CD4 T cells were observed in active TAK patients than those in healthy controls (all P < 0.01). The levels of IL-9 had a positive correlation with ESR ( r = 0.975, P = 0.015) in these cases. Our data suggested that Th9 cells and IL-9 could possibly be involved in the pathogenesis of TAK. [ABSTRACT FROM AUTHOR]

Asthma is a serious health and socioeconomic issue all over the world, affecting more than 300 million individuals. The disease is considered as an inflammatory disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus hyper-production and airway wall remodeling. The presence of airway inflammation in asthmatic patients has been found in the 19th century. As the information in patients with asthma increase, paradigm change in immunology and molecular biology have resulted in an extensive evaluation of inflammatory cells and mediators involved in the pathophysiology of asthma. Moreover, it is recognized that airway remodeling into detail, characterized by thickening of the airway wall, can be profound consequences on the mechanics of airway narrowing and contribute to the chronic progression of the disease. Epithelial to mesenchymal transition (EMT) plays an important role in airway remodeling. These epithelial and mesenchymal cells cause persistence of the inflammatory infiltration and induce histological changes in the airway wall, increasing thickness of the basement membrane, collagen deposition and smooth muscle hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling leads to the airway wall thickening and induces increased airway smooth muscle mass, which generate asthmatic symptoms.Asthma is classically recognized as the typical Th2 disease, with increased IgE levels and eosinophilic inflammation in the airway. Emerging Th2 cytokines modulates the airway inflammation, which induces airway remodeling. Biological agents, which have specific molecular targets for these Th2 cytokines, are available and clinical trials for asthma are ongoing. However, the relatively simple paradigm has been doubted because of the realization that strategies designed to suppress Th2 function are not effective enough for all patients in the clinical trials. In the future, it is required to understand more details for phenotypes of ast

The ETS family transcription factor PU.1 is one of the best-studied regulators of hematopoiesis. While research over the past two decades has established that PU.1 is essential for many aspects of lymphoid and myeloid cell development, the more recent development of the tools that enable PU.1 function to be assessed in adult mice and in specific cell lineages has led to the discovery of some surprising new roles of this versatile factor in the adaptive immune response. Despite being required for fetal lymphopoiesis, PU.1 is dispensable for the differentiation of committed B cells. There is, however, an emerging and still uncharacterized function of PU.1 as a repressor for late B-cell differentiation. In contrast, PU.1 is required at every point for the differentiation of all dendritic cells, in part, although its regulation of the crucial receptor Flt3. Within the T-cell lineage, PU.1 is required for the earliest thymic development, although the mechanism remains unknown, while recent studies have shown a previously unknown function of PU.1 in peripheral T-cell differentiation. Here, we review insights derived from these mouse models of PU.1 deficiency, with particular emphasis on these functions of PU.1 in the lymphocyte and dendritic cell lineages. [ABSTRACT FROM AUTHOR]

• Neobavaisoflavone suppresses the IL-9 production of CD4+ T cells in vitro. • Neobavaisoflavone decreases T H 9 cell differentiation in a PU.1 dependent manner. • Neobavaisoflavone alleviates DSS-induced colitis. • Neobavaisoflavone protects mice from colitis by targeting T H 9 cells. • Neobavaisoflavone inhibits human T H 9 cell differentiation in vitro. Neobavaisoflavone (Neo), is the active constituent of the herb Psoralea corylifolial , used in the traditional Chinese medicine, and has anti-inflammatory activity, but whether Neo could regulate colitis remains unclear. T helper 9 (T H 9) cells, a subset of CD4+ T helper cells characterized by secretion of IL-9, have been reported to be involved in the pathogenesis of many autoimmune and inflammatory diseases, but whether Neo could control T H 9 cell differentiation also remains unclear. Here, we found that Neo could decrease IL-9 production of CD4+ T cells by targeting PU.1 in vitro. Importantly, Neo had therapeutic effects on DSS-induced colitis. Furthermore, we identified T H 9 cells as the direct target of Neo for attenuating bowel inflammation. Therefore, Neo could serve as a lead for developing new therapeutics against inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

TH9 cells join the ever-growing list of CD4+ T helper subsets and primarily mediate anti-parasite immune responses. We have recently demonstrated that tumor-specific TH9 cells induce a CCL20-CCR6-dependent regulation of DCs while stimulating CD8+ T cell-mediated antitumor immunity. These findings offer a novel immunotherapeutic strategy against cancer. [ABSTRACT FROM AUTHOR]

• Platelet specific CD4+ T cells are required for anti-platelet antibody production. • Th1/Th2 immune deviation is directly implicated in ITP development and progression. • Th17 cells and platelets have multifaceted and pro-active mutual relationship. • Both numerical and functional abnormalities of Tregs were observed in ITP patients. • Th22, Th9 and Tfh cells could be also associated with ITP pathophysiology. Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts due to enhanced platelet clearance and compromised production. Traditionally, ITP was regarded a B cell mediated disorder as anti-platelet antibodies are detected in most patients. The very nature of self-antigens, evident processes of isotype switching and the affinity maturation of anti-platelet antibodies indicate that B cells in order to mount anti-platelet immune response require assistance of auto-reactive CD4+ T cells. For a long time, ITP pathogenesis has been exclusively reviewed through the prism of the disturbed balance between Th1 and Th2 subsets of CD4+ T cells, however, more recently new subsets of these cells have been described including Th17, Th9, Th22, T follicular helper and regulatory T cells. In this paper, we review the current understanding of the role and immunological mechanisms by which CD4+ T cells contribute to the pathogenesis of ITP. [ABSTRACT FROM AUTHOR]

Background: Th9 cells have been implicated in the development of allergic inflammation, though its contribution to allergic rhinitis and the effect of steroid on Th9 cell-mediated nasal responses are unclear., Objective: In this study, allergen-induced nasal inflammatory responses and their steroid responsiveness were investigated in ovalbumin (OVA)-specific Th9 cell-transferred mice., Methods: BALB/c mice were transferred with in vitro -differentiated Th9 cells and challenged by intranasal injection of OVA with or without subcutaneous administration of dexamethasone (Dex). Then, the infiltration of inflammatory cells in the nasal mucosa and nasal hyperresponsiveness (NHR) was assessed., Results: The significant NHR accompanied by nasal infiltration of eosinophils as well as allergen-specific T cells was induced in Th9 cell-transferred mice upon allergen challenge. These responses were strongly suppressed by the treatment with Dex., Conclusion: The participation of Th9 cells in the pathogenesis of allergic rhinitis was suggested., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2021. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

• Th9 cells are present in resected tumors from CRC patients. • IL-9-expression was subjected to PD-1/PD-L1-mediated suppression. • Th9 cells were induced from circulating CXCR3−CCR6− CD4+ T cells via TGF-β and IL-4. • Th9 cells promoted the expansion of CD8+ T cells in an IL-9R-dependent fashion. • IL-9-expressing TIL frequencies in tumor were associated with CD8+ TIL frequencies. Th9 cells are named after their expression of IL-9. Studies in recent years demonstrated that Th9 cells could contribute to antitumor immunity by enhancing the recruitment and activation of mast cells, natural killer cells, CD8 T cells, and dendritic cells in the tumor microenvironment. To determine whether Th9 cells participate in colorectal cancer (CRC), we collected resected tumor samples from 20 CRC patients. In the tumor-infiltrating lymphocytes (TILs), IL-9+IL-4− CD4+ T cells could be observed and were present at higher frequencies than the IL-9+IL-4+ and the IL-9−IL-4+ cells, suggesting that the majority of IL-9-producing TILs were bona fide Th9 cells. IL-9-secreting TILs presented particularly high PD-1 expression directly ex vivo. The expression of IL-9 was significantly reduced with PD-L1-mediated inhibition, which in turn was suppressed by anti-PD-1 blocking. Interestingly, the circulating CD4+ T cell compartment in CRC patients also presented Th9 enrichment, characterized by higher IL-9+IL-4− and IL-9+IL-4+ cell frequencies in the CXCR3−CCR6− compartment as compared to that in non-cancer controls. Using exogenous TGF-β and IL-4, we were capable of enriching Th9 cells without concurrent enrichment of Th2 cells. Th9-enriched CD4+ T cells, but not Th9-non-enriched cells, significantly increased the expansion of activated CD8+ T cells, in a manner that was dependent on the expression of IL-9R. In addition, the frequencies of Th9 cells in the tumor were positively correlated with the frequencies of CD8+ TILs. Together, we demonstrated that Th9 cells infiltrated CRC tumor, could be regulated via the PD-1/PD-L1 pathway, and could contribute the CD8+ T cell expansion. [ABSTRACT FROM AUTHOR]

Objective: To detect the expression level of ICOS on Th9 cells in mice infected with Schistosoma japonicum , and investigate the relation between ICOS signaling and Th9 cell polarization., Methods: Twenty-five mice with S. japonicum infection were used as models. IL-9 + cells in CD4 + T cells and ICOS + cells in Th9 cells of the mice were detected by flow cytometry 0, 4, 7, 9 weeks and 12 weeks after the infection., Results: Compared with that 0 week after the infection, the proportion of Th9 cells in CD4 + T cells of the mice significantly increased 4, 7, 9, 12 weeks after the infection (all P < 0.05), and the proportion of ICOS + cells in Th9 cells also markedly improved ( P < 0.05)., Conclusions: In S. japonicum infection, the ICOS signaling may have a regulatory effect on Th9 cell polarization.

TH9 cells have been implicated in triggering antitumor immunity. We have identified that GITR co-stimulation inhibits iTregcell generation but drives TH9 cell differentiation, thereby suppressing tumor growth via enhancing the function of DCs and CTLsin vivo. Our findings provide novel mechanisms by which GITR agonists exert antitumor activity. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) is one of the major infectious diseases in which CD4+ T helper (Th) cells play a crucial role. Th9 cells are a distinct subset of CD4+ Th cells with important physiological functions., Objective: The study aimed to assess the potential involvement of Th9 cells in the inadequate immune response leading to chronic HBV infection., Patients and Methods: Peripheral blood samples were collected from 22 CHB patients and 16 healthy controls (HC). The frequencies of circulating Th9, Tc9, Th1, and Tc1 cells were determined by flow cytometry. Serum levels of IL-9 and IL-10 were analyzed by ELISA. Serum biochemical indices of liver function were measured using an automated analyzers. Serum HBV DNA loads were analyzed by real-time PCR. The potential association of the frequency of Th9, Tc9, Th1 or Tc1 cells with clinical parameters was assessed., Results: The frequency of circulating Th9 cells was significantly lower in CHB patients than those in HC. However, no significant differences in the frequency of Tc9, Th1 or Tc1 cells were observed between the two groups. The percentages of Th9 cells, but not Tc9 cells, were negatively correlated with HBV DNA loads, whereas the percentages of Tc1 cells were positively correlated with viral loads in CHB patients. Moreover, there was a positive correlation between serum levels of IL-9 and IL-10 and HBV DNA loads in patients with chronic HBV infection., Conclusion: The depletion of Th9 cells is associated with the development of chronic HBV infection., (© 2017 Wiley Periodicals, Inc.)