Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence.

Zindl, Carlene L; Wilson, C Garrett; Chadha, Awalpreet S; Duck, Lennard W; Cai, Baiyi; Harbour, Stacey N; Nagaoka-Kamata, Yoshiko; Hatton, Robin D et al. · Nature · 2024

basic_science · Level V

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Abstract

Interleukin 22 (IL-22) has a non-redundant role in immune defence of the intestinal barrier<sup>1-3</sup>. 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<sup>4</sup> (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.

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