Deletion of IRF4 in Dendritic Cells Leads to Delayed Onset of T Cell-Dependent Colitis.

Classical dendritic cells (cDC) can be classified into two major subsets: Irf8-dependent cDC1 and Irf4-expressing cDC2. Although these subsets play distinct roles in intestinal immune homeostasis, their functions in T cell-driven colitis remain unknown. To assess the role of IRF4 expression in cDC2 in T cell-driven colitis, CD11c-Cre.Irf4^fl/fl and Irf4^fl/fl mice were backcrossed onto a Rag-1^-/- background and used as recipients of CD45RB^hiCD4⁺ T cells. Colitis score and innate immune cell influx were reduced in Cre⁺ mice 4 wk posttransfer, and these changes were associated with reduced CD4⁺ T cell counts in both the mesenteric lymph nodes and colon. By 7 wk, colitis score and colon CD4⁺ T cell numbers were similar in Cre⁺ and Cre^- mice despite a selective reduction in Th17 cells in the colon of Cre⁺ mice and a continued reduction in CD4⁺ T cell numbers in mesenteric lymph nodes. Cotransfer of CD25⁺CD45RB^lo CD4⁺ T cells prevented CD45RB^hiCD4⁺ T cell-driven colitis in both Cre⁺ and Cre^- recipients, demonstrating that IRF4 expression by cDC is not required for CD4⁺ regulatory T cell-mediated control of colitis. Collectively these results suggest a role for IRF4 expression in cDC2 in the generation of colitogenic CD4⁺ T cells, which becomes redundant as colitis progresses.

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