A novel subset of colonocytes targeted by Citrobacter rodentium elicits epithelial MHCII-restricted help from CD4 T cells

Interleukin (IL)-22 plays a non-redundant role in immune defense of the intestinal barrier[1][1]–[3][2]. 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][3]. 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. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-3 [3]: #ref-4