A novel subset of colonocytes targeted by Citrobacter rodentium elicits epithelial MHCII-restricted help from CD4 T cells
Zindl, C.; Wilson, C. G.; Chadha, A.; Cai, B.; Harbour, S.; Nagaoka-Kamata, Y.; Hatton, R.; Gao, M.; Figge, D.; Weaver, C.
Show abstract
Interleukin (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 by C.r and 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 resist C.r invasion. Our findings explain the basis for the regionalization of the host response to C.r and demonstrate that epithelial cells must elicit MHCII-dependent help from IL-22-producing T cells to orchestrate immune protection in the intestines.
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