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.

IRF5多态性与多种免疫介导的疾病相关，包括溃疡性结肠炎。IRF5 的贡献归因于它在骨髓谱系中的作用。T 细胞固有的 IRF5 如何导致炎症结果尚不清楚。我们确定了 T 细胞固有 IRF5 以前未定义的关键作用。^{在小鼠中，CD4 +} T 细胞中的 IRF5促进 Th1 和 Th17 相关细胞因子并减少 Th2 相关细胞因子。IRF5 是早期 TCR 启动的信号复合物和下游信号的最佳组装所必需的，并且在后期与 Th1 和 Th17 相关转录因子和细胞因子的启动子结合。IRF5 还调节趋化因子受体启动的信号转导，进而调节 T 细胞迁移。在体内，CD4 中的 IRF5⁺ T 细胞增强了实验性结肠炎的严重程度。重要的是，来自高 IRF5 表达疾病风险遗传携带者的人类 CD4 ⁺ T 细胞表现出增加的趋化因子诱导的迁移和 Th1/Th17 细胞因子以及减少的 Th2 相关和抗炎细胞因子。这些数据证明了 T 细胞固有 IRF5 在炎症结果中的关键作用。