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

doi:10.1038/s41586-024-07288-1

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

Nature. 2024 Apr 10. doi: 10.1038/s41586-024-07288-1. Online ahead of print.

Authors

Affiliations

¹ Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. carlenezindl@uabmc.edu.
² Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
³ Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴ Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. cweaver@uabmc.edu.

^# Contributed equally.

PMID: 38600382
DOI: 10.1038/s41586-024-07288-1

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 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.