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

• Main Authors: Jie Yan, Surya P. Pandey, Betsy J. Barnes, Jerrold R. Turner, Clara Abraham
• Format: Article
• Language: English
• Published: Elsevier 2020-06-01
• Series: Cell Reports
• Subjects: T cells; colitis; IRF5; cytokines; T cell trafficking; inflammatory bowel disease
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124720308019

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 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.