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SRC2 controls CD4+ T cell activation via stimulating c-Myc-mediated up-regulation of amino acid transporter Slc7a5

ABSTRACT: Purpose: Since SRC2 is a transcriptional co-activator that is believed to regulate cellular function by controlling gene expression, RNA-seq analysis was performed to detect the transcriptome of SRC2fl/fl and SRC2fl/fl/CD4-Cre CD4+ cells 4 weeks post adoptive transferred to Rag1-/-

ORGANISM(S): Mus musculus

PROVIDER: GSE229633 | GEO | 2023/05/01

REPOSITORIES: GEO

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SRC2 controls CD4+ T cell activation via stimulating c-Myc-mediated up-regulation of amino acid transporter Slc7a5

Project description:SRC2 controls CD4+ T cell activation via stimulating c-Myc-mediated up-regulation of amino acid transporter Slc7a5

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Steroid nuclear receptor coactivator 2 controls immune tolerance by promoting induced Treg differentiation via upregulating Nr4a2

Project description:Purpose:Steroid nuclear receptor coactivator 2 (SRC2) is a member of family of transcription co-activators. While SRC1 inhibits the differentiation of regulatory T cells (Tregs) critical for establishing immune tolerance, we show here that SRC2 stimulates Treg differentiation. SRC2 is dispensable for the development of thymic Tregs, whereas naïve CD4+ T cells from mice deficient of SRC2 specific in Tregs (SRC2fl/fl/Foxp3YFP-Cre) display defective Treg differentiation. Furthermore, the aged SRC2fl/fl/Foxp3YFP-Cre mice spontaneously develop autoimmune phenotypes including enlarged spleen and lung inflammation infiltrated with IFNγ-producing CD4+ T cells. SRC2fl/fl/Foxp3YFP-Cre mice also develop severer experimental autoimmune encephalomyelitis (EAE) due to reduced Tregs. Mechanically, SRC2 recruited by NFAT1 binds to the promoter and activates the expression of Nr4a2 which then stimulates Foxp3 expression to promote Treg differentiation. Members of SRC family co-activators thus play distinct roles in Treg differentiation and are potential drug targets for controlling immune tolerance

2022-04-30 | GSE201431 | GEO

GATA3 induces the pathogenicity of Th17 cells via regulation of GM-CSF expression

Project description:To investigate the effects of a late deletion of Gata3 on CD4 T cell gene expression profiles in experimental autoimmune encephalomyelitis, we performed a RNA-Seq analysis of Gata3-sufficient (i.e., Cd45.1/Cd45.2 or vehicle treated Cd45.2/Cd45.2 Cre-ERT2 Gata3 fl/fl) and Gata3-deficient (i.e., tamoxifen-treated Cd45.2/Cd45.2 Cre-ERT2 Gata3 Fl/Fl) CNS-infiltrating CD4+ effector T cells from mixed congenic co-transfer recipient mice. We performed a gene expression profiling analysis using data obtained from RNA-seq from 2 mixed congenic adoptive transfer receipient vehicle-treated mice and 2 mixed congenic adoptive transfer receipient tamoxifen-treated mice for a total of 8 biological samples.

2023-06-20 | GSE227394 | GEO

Transcriptome analysis of CD4+ T cells in experimental autoimmune encephalitomyelitis

Project description:In this study we determined whole genome gene expression of murine naive CD4+ T cells, in vitro differentiated Th17 cells, and CD4+ T cells isolated from experimental autoimmune encephalitomyelitis (EAE)-affected animals either after adoptive transfer of Th17 cells or after immunization with MOG35-55-peptide. The overall goal was to identify candidate genes involved in T cell pathology, encephalitogenicity and plasticity. These findings could then be correlated to multiple sclerosis pathology. Naive CD4+ T cells were isolated from B6.2d2 transgenic mice with MOG-specific T cell receptors and differentiated in vitro into Th17 cells. These Th17 cells were adoptively transferred into lymphopenic RAG1-/- mice to induce EAE. Further, EAE was induced by immunizing wild-type C57BL/6 mice with MOG35-55 peptide. RNA was extracted from naive CD4+ T cells, Th17 cells, and from CD4+ T cells isolated from the CNS of EAE-affected mice for gene expression analysis. Replicates from three independent experiments were analyzed.

2015-02-26 | E-GEOD-57098 | biostudies-arrayexpress

The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids

Project description:This SuperSeries is composed of the SubSeries listed below. CD4+ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4+ T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn?s disease-like ileitis following transfer into Rag1-/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1-/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn?s disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis.

2020-01-10 | GSE143405 | GEO

Role of the metabolic sensor AMP-activated protein kinase in T cell function in vivo [TCR-seq]

Project description:Purpose: To investigate the function of AMPK in T cells during in vivo activation. Methods: WT (PRKAA1fl/fl) and KO (CD4-Cre PRKAA1fl/fl) T cells were transferred into Rag KO recipients to induce adoptive T cell transfer mediated colitis. Donor WT and KO spleen and mLN T cells were isolated 6 weeks after transfer and gene expression was assessed in WT vs. KO T cells and spleen vs. mLN samples.

2021-06-04 | GSE152156 | GEO

Role of the metabolic sensor AMP-activated protein kinase in T cell function in vivo [RNA-seq]

2021-06-04 | GSE152151 | GEO

The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids [Rh123hi-lo RNA-Seq]

Project description:CD4+ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4+ T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn’s disease-like ileitis following transfer into Rag1-/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1-/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn’s disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis.

2020-01-10 | GSE143404 | GEO

The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids [shMdr1 RNA-seq in vivo]

2020-01-10 | GSE143403 | GEO

SRC2 and SRC3 cooperatively promote pathogenic function of Th17 cells via regulation of epigenetic activation

Project description:Steroid receptor coactivator 3 (SRC3) was reported to regulates pathogenic Th17 cell differentiation in vitro and in vivo.However, the role of SRC2, another member of SRC family, and its relationship with SRC3 in the regulation of Th17 cell differentiation remain unknown. We used RNA-seq to study the global function of SRC2 and SRC3. Naive CD4+ T cells were activated with 5ug/ml plate-bound anti-CD3/28, and cultured with TGF-β+IL-6 or with IL-6+IL-1β+IL23. 4days later, cells were restimulated with plate-bound anti-CD3 for 4hrs for RNA-seq.

2022-07-20 | GSE133641 | GEO

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