Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis

By L. Durant, W. Watford, Haydeé L. Ramos, A. Laurence, G. Vahedi, Lai Wei, H. Takahashi1, Hong-Wei Sun, Y. Kanno, F. Powrie and 1 more. Immunity, 2010

740 citations recorded by the source corpus.

Summary 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.

Subfields: Genetics, Immunology

View Paper: https://www.semanticscholar.org/paper/db7b7c36328ac94544d2ebbcab9fa96c623d8e8d

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Citations in the corpus

JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. (2012, background): “What emerges is that STATs have thousands of genomic targets and have major effects on transcription and epigenetic modifications (Durant et al., 2010; Elo et al., 2010; Good et al., 2009; Liao et al., 2011a; Wei et al., 2010).”
Molecular Mechanisms of Treg-Mediated T Cell Suppression (2012, background): “Thus, loss of STAT3 expression in T cells during T cell transfer-induced colitis and systemic inflammation increased Treg induction and ameliorated disease (Durant et al., 2010).”
Opposing regulation of the Il17 locus through direct, reciprocal actions of STAT3 and STAT5 (2011, background): “STAT3 directly regulates the locus encoding IL-17 (genes Il17a – Il17f ; collectively called ' Il17 ' here) and is necessary for the expression of many transcription factors involved in T H 17 differentiatio”
Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation (2011, neutral): “STAT3 has recently been shown to directly bind to a diverse array of targets (Durant et al., 2010).”
Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. (2011, neutral): “Furthermore, although Stat3 binds most of the genes that have been shown to promote TH17 cell fate determination, it also binds to many genes that are involved in T cell survival and proliferation (Durant et al., 2010).”
Peripheral CD4 T cell differentiation regulated by networks of cytokines and transcription factors (2010, background): “Both RORct and STAT3 bind to multiple sites in the Il17a ⁄ Il17f locus including the promoters of these cytokines (80, 82, 164, 165).”
The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention (2015, background): “STAT3 directly binds many of the key genes required for Th17 differentiation, including the Il17 gene itself (9, 10).”