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Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells [ChIP-seq]

ABSTRACT: Stress elicits inflammatory and autoimmune diseases while concurrently triggering the production of glucocorticoids (GCs), renowned for their anti-inflammatory effects. In addition, IL-17-producing helper T (Th17) cells are pivotal in initiating inflammation and certain autoimmune disorders. However, whether stress-induced GCs exacerbate inflammatory and autoimmune diseases through Th17 cells remains elusive. Here, we show that GCs facilitate the differentiation and survival of Th17 cells in mice. GCs inhibit the expression of TCF1, a negative regulator of Th17 cell differentiation, thereby increasing pathogenic TCF1low Th17 cells characterized by high glycolytic activity. Remarkably, mice lacking the glucocorticoid receptor (GR), specifically in  T cells, manifest less severe experimental autoimmune encephalomyelitis (EAE) and inflammatory colitis. Moreover, stress-induced GCs augment the population of Th17 cells, intensify their IL-17 production, and provoke neutrophil recruitment, resulting in severe inflammation and substantial weight loss in the colitis model. This study demonstrates that stress-induced GCs exacerbate inflammation and autoimmunity by fostering Th17 cell differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE235250 | GEO | 2025/07/31

REPOSITORIES: GEO

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Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells [mTh17_RNAseq]

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Project description:STAT3, an essential transcription factor with pleiotropic functions, plays critical roles in the pathogenesis of autoimmunity. Despite recent data linking STAT3 with inflammatory bowel disease, exactly how it contributes to chronic intestinal inflammation is not known. Using a T cell transfer model of colitis we found that STAT3 expression in T cells was essential for the induction of both colitis and systemic inflammation. STAT3 was critical in modulating the balance of T helper 17 (Th17) and regulatory T (Treg) cells, as well as in promoting CD4+ T cell proliferation. We used chromatin immunoprecipitation and massive parallel sequencing (ChIP-Seq) to define the genome-wide targets of STAT3 in CD4+ T cells. We found that STAT3 bound to multiple genes involved in Th17 cell differentiation, cell activation, proliferation and survival, regulating both expression and epigenetic modifications. Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis. This SuperSeries is composed of the following subset Series: GSE21669: Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis [ChIP-seq] GSE21670: Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis [Affymetrix Expression] Refer to individual Series

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