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 and Casey T. Weaver ()
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Carlene L. Zindl: Heersink School of Medicine, University of Alabama at Birmingham
C. Garrett Wilson: Heersink School of Medicine, University of Alabama at Birmingham
Awalpreet S. Chadha: University of Alabama at Birmingham
Lennard W. Duck: University of Alabama at Birmingham
Baiyi Cai: Heersink School of Medicine, University of Alabama at Birmingham
Stacey N. Harbour: Heersink School of Medicine, University of Alabama at Birmingham
Yoshiko Nagaoka-Kamata: Heersink School of Medicine, University of Alabama at Birmingham
Robin D. Hatton: Heersink School of Medicine, University of Alabama at Birmingham
Min Gao: University of Alabama at Birmingham
David A. Figge: Heersink School of Medicine, University of Alabama at Birmingham
Casey T. Weaver: Heersink School of Medicine, University of Alabama at Birmingham

Nature, 2024, vol. 629, issue 8012, 669-678

Abstract: Abstract Interleukin 22 (IL-22) has a non-redundant role in immune defence of the intestinal barrier1–3. 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 rodentium4 (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.

Date: 2024
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DOI: 10.1038/s41586-024-07288-1

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