T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation

T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation

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Summary: 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 saxemodel 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 anodized pearl price xbox 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.