Similar Datasets
Project description:IL-17-producing gd T (Tgd17) cells are early mediators of immunity and autoimmunity that undergo effector programming in the thymus. While Vg subset-restricted regulators of Tgd17 specialization are known, a universal type 17 commitment factor for all gd T cells remains undefined. In this study, we identify the transcription factor c-Maf as an essential and uniform regulator of Tgd17 differentiation and maintenance. The absolute lineage block caused by Maf deficiency reveals a critical effector acquisition checkpoint at the immature CD24+ CD45RBlo gd thymocyte stage. Here, c-Maf enforces Tgd17 identity by promoting chromatin accessibility and activating expression of lineage-defining RORgt and key type 17 program genes, while coordinately antagonizing the negative regulator TCF1, which promotes the alternative IFNg+ Tgd1 fate. During specialization, c-Maf expression is tuned by gdTCR signal strength, implicating c-Maf as a rheostat controlling effector gd T cell generation and connecting gdTCR signals to a core node in the Tgd17 network.
2018-12-03 | GSE120426 | GEO
Project description:IL-17-producing gd T (Tgd17) cells are early mediators of immunity and autoimmunity that undergo effector programming in the thymus. While Vg subset-restricted regulators of Tgd17 specialization are known, a universal type 17 commitment factor for all gd T cells remains undefined. In this study, we identify the transcription factor c-Maf as an essential and uniform regulator of Tgd17 differentiation and maintenance. The absolute lineage block caused by Maf deficiency reveals a critical effector acquisition checkpoint at the immature CD24+ CD45RBlo gd thymocyte stage. Here, c-Maf enforces Tgd17 identity by promoting chromatin accessibility and activating expression of lineage-defining RORgt and key type 17 program genes, while coordinately antagonizing the negative regulator TCF1, which promotes the alternative IFNg+ Tgd1 fate. During specialization, c-Maf expression is tuned by gdTCR signal strength, implicating c-Maf as a rheostat controlling effector gd T cell generation and connecting gdTCR signals to a core node in the Tgd17 network.
2018-12-03 | GSE120425 | GEO
Project description:γδ T cells that produce the cytokine IL-17 (Tγδ17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of Tγδ17 specialization restricted to various Vγ subsets are known, a commitment factor essential to all Tγδ17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of Tγδ17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24+CD45RBlo γδ thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced Tγδ17 cell identity by promoting chromatin accessibility and expression of key type 17 program genes, notably Rorc and Blk, while antagonizing the transcription factor TCF1, which promotes interferon-γ-producing γδ T cells (Tγδ1 cells). Furthermore, γδ T cell antigen receptor (γδTCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects γδTCR signals to Tγδ17 cell transcriptional programming.
| S-EPMC6294311 | biostudies-literature
Project description:c-Maf is an essential commitment factor for IL-17-producing gd T cells
| PRJNA493051 | ENA
Project description:c-Maf is an essential commitment factor for IL-17-producing gd T cells [RNA-seq]
| PRJNA493053 | ENA
Project description:c-Maf is an essential commitment factor for IL-17-producing gd T cells [ATAC-seq]
| PRJNA493056 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-04-08 | GSE228748 | GEO
Project description:IL-17 cytokine family members have diverse biological functions, promoting protective immunity against many pathogens but also driving inflammatory pathology during infection and autoimmunity. IL-17A and IL-17F are produced by CD4+ and CD8+ T cells, γδ T cells, and various innate immune cell populations in response to IL-1β and IL-23, and they mediate protective immunity against fungi and bacteria by promoting neutrophil recruitment, antimicrobial peptide production and enhanced barrier function. IL-17-driven inflammation is normally controlled by regulatory T cells and the anti-inflammatory cytokines IL-10, TGFβ and IL-35. However, if dysregulated, IL-17 responses can promote immunopathology in the context of infection or autoimmunity. Moreover, IL-17 has been implicated in the pathogenesis of many other disorders with an inflammatory basis, including cardiovascular and neurological diseases. Consequently, the IL-17 pathway is now a key drug target in many autoimmune and chronic inflammatory disorders; therapeutic monoclonal antibodies targeting IL-17A, both IL-17A and IL-17F, the IL-17 receptor, or IL-23 are highly effective in some of these diseases. However, new approaches are needed to specifically regulate IL-17-mediated immunopathology in chronic inflammation and autoimmunity without compromising protective immunity to infection.
| S-EPMC9255545 | biostudies-literature
Project description:IL-10 is an important immunoregulatory factor. However, our understanding of IL-10 gene regulation remains very limited. In this study, following up on our previous novel finding that the protooncogene c-Maf of the basic leucine zipper family of transcription factors is expressed in monocytes and macrophages, we investigate the role of c-Maf in the transcriptional regulation of IL-10 and the underlying molecular mechanism in macrophages. c-Maf-null macrophages exhibit strongly impaired IL-10 protein production and mRNA expression upon LPS stimulation. Ectopic expression of c-Maf stimulates not only exogenously transfected IL-10 promoter-driven luciferase activity in a dose-dependent manner but also enhances endogenous IL-10 gene expression stimulated by LPS. Both in vitro and in vivo experiments identify a c-Maf response element localized to nucleotides -196/-184 relative to the transcription initiation site in the IL-10 promoter. This site represents an atypical 12-O-tetradecanoate-13-acetate-responsive element for musculoaponeurotic fibrosarcoma recognition and functions as an enhancer element in a heterologous and orientation-independent manner. Furthermore, c-Maf is expressed constitutively in resting monocytes/macrophages. IL-4 can up-regulate c-Maf expression, its binding to IL-10 promoter, and dose dependently enhance IL-10 production induced by LPS; moreover, IL-4 failed to enhance LPS-induced IL-10 production in c-Maf-null macrophages. Taken together, these data demonstrate that c-Maf is an indispensable yet constitutive transcription factor for IL-10 gene expression in LPS-activated macrophages, and IL-4 modulates IL-10 production in inflammatory macrophages likely via its ability to induce c-Maf expression. Thus, this study uncovers a novel and important function of c-Maf in macrophages and elucidates its transcriptional mechanism in the regulation of IL-10 gene expression.
| S-EPMC2955976 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-11-20 | GSE189232 | GEO