| First Author | Yan J | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 13 | Pages | 107820 |
| PubMed ID | 32610123 | Mgi Jnum | J:302001 |
| Mgi Id | MGI:6489206 | Doi | 10.1016/j.celrep.2020.107820 |
| Citation | Yan J, et al. (2020) T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation. Cell Rep 31(13):107820 |
| abstractText | 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. |
