Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence
Carlene L. Zindl, C. Garrett Wilson, Awalpreet S. Chadha, Lennard W. Duck, Baiyi Cai, Stacey N. Harbour, Yoshiko Nagaoka-Kamata, Robin D. Hatton, Min Gao, David A. Figge, Casey T. Weaver
Abstract
Abstract Interleukin 22 (IL-22) has a non-redundant role in immune defence of the intestinal barrier 1–3 . T cells, but not innate lymphoid cells, have an indispensable role in sustaining the IL-22 signalling that is required for the protection of colonic crypts against invasion during infection by the enteropathogen Citrobacter rodentium 4 ( Cr ). However, the intestinal epithelial cell (IEC) subsets targeted by T cell-derived IL-22, and how T cell-derived IL-22 sustains activation in IECs, remain undefined. Here we identify a subset of absorptive IECs in the mid–distal colon that are specifically targeted by Cr and are differentially responsive to IL-22 signalling. Major histocompatibility complex class II (MHCII) expression by these colonocytes was required to elicit sustained IL-22 signalling from Cr -specific T cells, which was required to restrain Cr invasion. Our findings explain the basis for the regionalization of the host response to Cr and demonstrate that epithelial cells must elicit MHCII-dependent help from IL-22–producing T cells to orchestrate immune protection in the intestine.