| First Author | Pool L | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 4 | Pages | 1047-1055 |
| PubMed ID | 31900340 | Mgi Jnum | J:284041 |
| Mgi Id | MGI:6389003 | Doi | 10.4049/jimmunol.1900775 |
| Citation | Pool L, et al. (2020) Deletion of IRF4 in Dendritic Cells Leads to Delayed Onset of T Cell-Dependent Colitis. J Immunol 204(4):1047-1055 |
| abstractText | 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(hi)CD4(+) 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(hi)CD4(+) 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. |
