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Regulation of pathogenic T helper 17 cell differentiation by steroid receptor coactivator-3

ABSTRACT: Regulation of pathogenic T helper 17 cell differentiation by steroid receptor coactivator-3

PROVIDER: PRJNA454478 | ENA |

REPOSITORIES: ENA

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Regulation of pathogenic T helper 17 cell differentiation by steroid receptor coactivator-3

Project description:T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORgt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here we show that the steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarrays were used to showed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORtdependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical in RORt-dependent gene expression during Th17 cell-driven autoimmune diseases.

2018-05-02 | GSE113927 | GEO

Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

Project description:RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of steroid receptor coactivator-2/nuclear receptor coactivator 2 (SRC-2/NCOA2)

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A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

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Genome-wide Profiling of Steroid Receptor Coactivator 2 in mouse liver

Project description:Steroid Receptor 2 (SRC-2) is a coactivator involved in hepatic metabolism. To better understand its temporal involvement in metabolism genome wide profiling was performed at 2 time ZT4 and ZT18 as well as in the SRC-2 knockout mouse.

2014-11-10 | GSE53039 | GEO

Tissue- and Pathway-Specific Metabolomic Profiles of the Steroid Receptor Coactivator (SRC) family

Project description:The rapidly growing family of coregulators of nuclear receptors includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have begun to emerge as important regulators of metabolic homeostasis, including the p160 Steroid Receptor Coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis in liver and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of SRC family members, we have performed targeted metabolomics analysis of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockout of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 knockout mice and their wild-type littermates in the fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC coactivator. Overall, we observed entire groups or subgroups of metabolites belonging to discrete metabolic pathways that were influenced in different tissues and/or feeding states due to ablation of individual SRC isoforms. Surprisingly, we identified very few metabolites that changed universally across the three SRC knockout models. These findings demonstrate that coactivator function has very limited redundancy even within the homologous SRC coactivator family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.

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Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

Project description:Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

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Retinal pigment epithelial cells suppress interleukin-17-producing T-helper 17 cells

Project description:T cells that encounter cultured ocular pigment epithelial cells in vitro are inhibited from undergoing T cell receptor-triggered activation. Because retinal pigment epithelial (RPE) cells are able to suppress T-cell activation, we studied whether RPE cells could suppress cytokine production by activated T helper (Th) cells. In this study we showed that primary cultured RPE cells greatly suppressed activation of bystander CD4+ T cells in vitro, especially the cytokine production by the target T helper cells (Th1 cells, Th2 cells, Th17 cells, but not Th3 cells). Cultured RPE cells and RPE-supernatants significantly suppressed IL-17 producing CD4+ T cells, and RPE cells fully suppressed polarized Th17 cell lines that induced by recombinant proteins, IL-6 and TGFb2. Moreover, RPE cells failed to suppress IL-17 producing T cells in the presence of rIL-6. In addition, Th17 cells exposed to RPE were suppressed via TGFb, which produce RPE cells. These results indicate that retinal PE cells have immunosuppressive capacity in order to inhibit Th17-type effector T cells. Thus, ocular resident cells play a role in establishing immune regulation in the eye. Retinal pigment epithelium suppresses Th17 cells

2012-07-11 | E-GEOD-22877 | biostudies-arrayexpress

Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enalbles Murine Embryo Implantation

Project description:Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enalbles Murine Embryo Implantation

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Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enalbles Murine Embryo Implantation

Project description:Using conditional knockout technology, we demonstrate that steroid receptor coactivator-2 (SRC-2) is essential for development of the receptive uterus for embryo implantation. Through bulk RNA-seq analysis, we reveal that endometrial SRC-2 is required for not only the induction of the expression of established genes associated with uterine receptivity but also for the expression of genes involved in endometrial epithelial changes that enable attachment and invasion of the embryo into the underlying stroma. Together, these RNA-seq results underscore the importance of SRC-2 as a transcriptional coregulator in the endometrium during the periimplantation period.

2023-11-20 | GSE237740 | GEO

Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis.

Project description:Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis.

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