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.Irf4fl/fl and Irf4fl/fl mice were backcrossed onto a Rag-1-/- background and used as recipients of CD45RBhiCD4+ 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+CD45RBlo CD4+ T cells prevented CD45RBhiCD4+ 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.

Rivollier, AymericTechnical University of Denmark(Swepub:lu)med-ayr (författare)
Agace, William WLund University,Lunds universitet,Slemhinnans immunologi,Forskargrupper vid Lunds universitet,Mucosal Immunology,Lund University Research Groups,Technical University of Denmark(Swepub:lu)immu-wag (författare)
Technical University of DenmarkSlemhinnans immunologi (creator_code:org_t)

Ingår i:Journal of immunology: The American Association of Immunologists204:4, s. 1047-10551550-66060022-1767

Av författaren/redakt...: Pool, Lieneke; Rivollier, Aymer ...; Agace, William W

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