Publication Date

2020

Journal Title

Cell Rep

Abstract

© 2020 The Author(s) IRF5 polymorphisms are associated with multiple immune-mediated diseases, including ulcerative colitis. IRF5 contributions are attributed to its role in myeloid lineages. How T cell-intrinsic IRF5 contributes to inflammatory outcomes is not well understood. We identify a previously undefined key role for T cell-intrinsic IRF5. In mice, IRF5 in CD4+ T cells promotes Th1- and Th17-associated cytokines and decreases Th2-associated cytokines. IRF5 is required for the optimal assembly of the TCR-initiated signaling complex and downstream signaling at early times, and at later times binds to promoters of Th1- and Th17-associated transcription factors and cytokines. IRF5 also regulates chemokine receptor-initiated signaling and, in turn, T cell migration. In vivo, IRF5 in CD4+ T cells enhances the severity of experimental colitis. Importantly, human CD4+ T cells from high IRF5-expressing disease-risk genetic carriers demonstrate increased chemokine-induced migration and Th1/Th17 cytokines and reduced Th2-associated and anti-inflammatory cytokines. These data demonstrate key roles for T cell-intrinsic IRF5 in inflammatory outcomes.

Volume Number

31

Issue Number

13

Pages

107820

Document Type

Article

Status

Faculty

Facility

School of Medicine

Primary Department

Molecular Medicine

Additional Departments

General Pediatrics

PMID

32610123

DOI

10.1016/j.celrep.2020.107820


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