A novel subset of colonocytes targeted byCitrobacter rodentiumelicits epithelial MHCII-restricted help from CD4 T cells

Abstract

AbstractInterleukin (IL)-22 plays a non-redundant role in immune defense of the intestinal barrier1–3. We recently discovered an indispensable role for T cells, but not ILCs, in sustaining IL-22 signaling required for protection of colonic crypts against invasion during infection by the enteropathogen,Citrobacter rodentium(C.r)4. However, identification of the intestinal epithelial cell (IEC) subsets targeted by T cell-derived IL-22 and how T cell-derived IL-22 sustains activation in IECs are undefined. Here, we identify a novel subset of absorptive IECs in the mid-distal colon that are differentially targeted byC.rand are differentially responsive to IL-22 signaling. Importantly, MHCII expression by these colonocytes was required to elicit T cell-activated IL-22 signaling necessary to resistC.rinvasion. Our findings explain the basis for the regionalization of the host response toC.rand demonstrate that epithelial cells must elicit MHCII-dependent help from IL-22–producing T cells to orchestrate immune protection in the intestines.