Ena-DATASET-QCMG-21-04-2021-07:26:43:836-1020 - samples
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ABSTRACT:
PROVIDER: EGAD00001007532 | EGA |
REPOSITORIES: EGA
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Project description:Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-γ; some Th1 cells can also be anti-inflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and anti-inflammatory Th1 cells is still elusive. Here we show that Bhlhe40-deficient CD4 Th1 cells produced less IFN-γ but substantially more IL-10 than wild type Th1 cells. Bhlhe40-mediated IFN-γ production was independent of transcription factor T-bet regulation. Mice with conditional deletion of Bhlhe40 in T cells succumbed to Toxoplasma gondii infection and blockage of IL-10 signaling during infection rescued these mice from death. Thus, our results demonstrate that transcription factor Bhlhe40 is a molecular switch for determining the fate of inflammatory and anti-inflammatory Th1 cells.
2018-05-10 | GSE103173 | GEO
Project description:GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-g and switch their phenotype to Th1. Here we show that in addition to T-bet, TF RUNX3 also contributes to the Th1 switch of ThGM cells. T-bet-deficient ThGM cells in the CNS of mice with EAE had low expression of RUNX3, and knockdown of RUNX3 expression in ThGM cells abrogated the Th1-inducing effect of IL-12. Comparison of ThGM and Th1 cell transcriptomes showed that ThGM cells expressed a set of TFs known to inhibit the development of other Th lineages. Lack of expression of lineage-specific cytokines and TFs by ThGM cells, together with expression of TFs that inhibit the development of other Th lineages, suggests that ThGM cells are a non-polarized subset of Th cells with lineage characteristics.
2022-07-27 | GSE205763 | GEO
Project description:IL-17 is a key cytokine important for defense against infection and plays a critical role in inflammatory diseases. To understand the diversity and identify a core gene signature among IL-17-producing T cell populations we isolated CD4+ and CD8+ IL-17 producing T cells for RNA sequencing.
2019-05-14 | GSE96741 | GEO
Project description:During chronic viral infection, the inflammatory function of CD4 T cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this T cell adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T cells during chronic infection. Unexpectedly, our analyses revealed an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T cells or deletion of Il10 specifically in Tfh cells resulted in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling was required for sustaining germinal center reactions. Lastly, we demonstrate that IL-27 and type I IFNs differentially regulate the formation of this protective IL-10-producing Tfh subset. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection.
2018-10-29 | GSE111026 | GEO
Project description:During chronic viral infection, the inflammatory function of CD4 T cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this T cell adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T cells during chronic infection. Unexpectedly, our analyses revealed an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T cells or deletion of Il10 specifically in Tfh cells resulted in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling was required for sustaining germinal center reactions. Lastly, we demonstrate that IL-27 and type I IFNs differentially regulate the formation of this protective IL-10-producing Tfh subset. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection.
2018-10-29 | GSE111025 | GEO
Project description:IL-6 has been proposed to favor the development of Th2 responses and play an important role in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation, differentiation and act as key player during inflammation and immune response. Th2 cytokines play an immunoregulatory role in early infection. Literature says in mice infected with L. major, IL-6 may promote the development of both Th1 and Th2 responses. IL-4 is also considered to be the signature cytokine of Th-2 response. IL6 was initially characterized as a Th1 cytokine but later on it was proved to be a pleiotropic cytokine, secreted from different cell types including the macrophages. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches may be used to tackle this challenge in an iterative process of quantitative mathematical analysis. In this study, we created an in silico model of IL6 mediated macrophage activation which suffers from an excessive impact of the negative feedback loop involving SOCS1. The strategy adopted in this framework may help to reduce the complexity of the leishmanial IL6 model analysis and also laydown various physiological or pathological conditions of IL6 signaling in future.
2024-09-02 | BIOMD0000000873 | BioModels
Project description:IL-4 plays an important role in the induction of Th2 and Th9 cells as well as in the inhibition of Th1 cell generation. We herein show that a combination of IL-4 and TGFbeta augment the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFNgamma is present. The T-box containing transcription factor, eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells, and is involved in IFNgamma production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFNgamma gene loci. TGFbeta is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6 signaling pathway. IFNgamma-producing CD103+ Th1 cells are detected in the IEL of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. These results represent the first molecular mechanism of IL-4/TGFbeta-dependent augmentation of Th1 cell generation, and raise the possibility that IL-4 and TGFbeta may simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions. CD103+ Th1 and Th1 cells are profiled for mRNA expression
2012-03-17 | E-GEOD-36520 | biostudies-arrayexpress
Project description:Control of the intracellular parasites that cause malaria and visceral leishmaniasis (VL) is dependent on the generation of pro-inflammatory, IFNγ+ Tbet+ CD4+ T (Th1) cells by infected hosts. Immunoregulatory IL-10 produced by Th1 cells serves to mitigate subsequent inflammation and related disease pathology. However, these IL-10-producing Th1 (Tr1) cells can also not only promote parasite persistence, but may impair immunity to re-infection and potential vaccine efficacy. Here, we identify molecular and phenotypic signatures that distinguish Th1 cells from Tr1 cells in both experimental VL, caused by infection of C57BL/6 mice with the human parasite Leishmania donovani, and in Plasmodium falciparum-infected humans participating in controlled human malaria infection (CHMI) studies. Such characterisations allow for the better understanding of Tr1 cell development and function in the context of these parasitic diseases, and for the identification of targets for immune modulation to improve anti-parasitic immunity.
| EGAS00001004454 | EGA
Project description:IL-4 plays an important role in the induction of Th2 and Th9 cells as well as in the inhibition of Th1 cell generation. We herein show that a combination of IL-4 and TGFbeta augment the development of Th1 cells that express CD103 (CD103+ Th1 cells) if IFNgamma is present. The T-box containing transcription factor, eomesodermin (Eomes) is preferentially expressed in CD103+ Th1 cells, and is involved in IFNgamma production. The induction of T-bet during early T cell activation is essential for the formation of the active chromatin at both the Eomes and IFNgamma gene loci. TGFbeta is required for the induction of Eomes and CD103, as well as the inhibition of Th2 cytokine expression. In addition, IL-4 induces Eomes transcription through activation of the Stat6 signaling pathway. IFNgamma-producing CD103+ Th1 cells are detected in the IEL of normal mice, and their numbers significantly decrease in Tbet- and Stat6-deficient mice. These results represent the first molecular mechanism of IL-4/TGFbeta-dependent augmentation of Th1 cell generation, and raise the possibility that IL-4 and TGFbeta may simultaneously enhance the Th1 cell-mediated immune responses under certain cytokine conditions. Th9+IFNgamma and Th9 cells are profiled for mRNA expression
2012-03-17 | E-GEOD-36554 | biostudies-arrayexpress
Project description:Interleukin (IL)-21 is essential for type 1 diabetes (T1D) development in the NOD mouse model. IL-21-expressing CD4 T cells are present in pancreatic islets where they contribute to disease progression. However, little is known about their phenotype and differentiation states. To fill this gap, we generated a novel IL-21 reporter NOD strain to further characterize IL-21+ CD4 T cells in T1D. IL-21+ CD4 T cells accumulate in pancreatic islets and recognize β-cell antigens. Single-cell RNA sequencing revealed that most CD4 T effector cells in islets actively express IL-21 and they are highly diabetogenic despite expressing multiple inhibitory molecules, including PD-1 and LAG3. Islet IL-21+ CD4 T cells segregate into four phenotypically and transcriptionally distinct differentiation states, less differentiated early effectors, Tfh-like cells, and two Th1 subsets. Trajectory analysis predicts that early effectors differentiate into both Tfh-like and terminal Th1 cells. We further demonstrated that intrinsic IL-27 signaling controls the differentiation of islet IL-21+ CD4 T cells, contributing to their helper function. Collectively, our study reveals the heterogeneity of islet-infiltrating IL-21+ CD4 T cells and indicates that both Tfh-like and Th1 subsets continuously produce IL-21 throughout their differentiation process, highlighting the important sources of IL-21 in T1D pathogenesis.
2023-01-30 | GSE212009 | GEO