JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation.

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2017-08-21

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Abstract

T helper 17 (Th17) cell plasticity contributes to both immunity and autoimmunity; however, the factors that control lineage flexibility are mostly unknown. Here we show the activator protein-1 (AP-1) factor JunB is an essential regulator of Th17 cell identity. JunB activates expression of Th17 lineage-specifying genes and coordinately represses genes controlling Th1 and regulatory T-cell fate. JunB supports Th17 cell identity by regulating key AP-1 complex constituents. In particular, JunB limits the expression of the subset repressor IRF8, and impedes access of JunD to regulatory regions of alternative effector loci. Although dispensable for homeostatic Th17 cell development, JunB is required for induction and maintenance of Th17 effector responses in the inflammatory contexts of both acute infection and chronic autoimmunity in mice. Through regulatory network analysis, we show that JunB is a core regulator of global transcriptional programs that promote Th17 cell identity and restrict alternative CD4+ T-cell potential.AP-1 family transcription factors regulate CD4+ T helper cell differentiation. Here the authors show that the AP-1 member JunB is a nonredundant regulator of transcriptional programs that support Th17 cell identity and restrain alternative Th1 and Treg cell fates in inflammatory contexts of acute fungal infection and chronic autoimmunity.

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10.1038/s41467-017-00380-3

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Carr, Tiffany M, Joshua D Wheaton, Geoffrey M Houtz and Maria Ciofani (2017). JunB promotes Th17 cell identity and restrains alternative CD4+ T-cell programs during inflammation. Nature communications, 8(1). p. 301. 10.1038/s41467-017-00380-3 Retrieved from https://hdl.handle.net/10161/19431.

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Ciofani

Maria Ciofani

Associate Professor of Integrative Immunobiology

Transcriptional Regulation of Proinflammatory Lymphocytes

IL-17-expressing CD4 T helper (Th17) cells are important members of the intestinal immune cell community that contribute to protection against bacterial and fungal infections, and maintenance of intestinal homeostasis.  Although central to immunity, dysregulted Th17 cell function has been implicated in tissue inflammation and autoimmune disease (e.g. Inflammatory bowel disease, arthritis, and multiple sclerosis).  In order to understand this balance between healthy and pathogenic responses, we are interested in defining the transcriptional regulatory mechanisms that govern (1) Th17 cell specification from naive T cell precursors and, (2) Th17 cell effector plasticity during inflammation.  Combining genome-wide interrogation of regulatory information (transcription factor occupancy, chromatin accessibility, and transcriptional output) with gene-deficiency models in mice, we can dissect the contribution of key transcriptional regulators in proinflammatory T cell function.



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