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

• Published in: Nature (London) Vol. 629; no. 8012; pp. 669 - 678
• Main Authors: Zindl, Carlene L., Wilson, C. Garrett, Chadha, Awalpreet S., Duck, Lennard W., Cai, Baiyi, Harbour, Stacey N., Nagaoka-Kamata, Yoshiko, Hatton, Robin D., Gao, Min, Figge, David A., Weaver, Casey T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.05.2024; Nature Publishing Group
• Subjects: 13; 13/1; 13/21; 13/31; 13/51; 13/95; 14; 631/250/2152; 631/326/41; Absorptivity; Animals; Antigens; Cell activation; Citrobacter; Citrobacter rodentium - immunology; Colon; Colon - cytology; Colon - immunology; Colon - microbiology; Cytokines; Defense; E coli; Enterobacteriaceae Infections - immunology; Enterobacteriaceae Infections - microbiology; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelium; Female; Genes; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Humanities and Social Sciences; Hyperplasia; Immune system; Infections; Interleukin 22; Interleukin-22 - immunology; Interleukin-22 - metabolism; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestine; Lymphocytes; Lymphocytes T; Lymphoid cells; Major histocompatibility complex; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; multidisciplinary; Pathogens; Science; Science (multidisciplinary); Signal Transduction - immunology; Small intestine; Stem cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-024-07288-1

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. The murine enteropathogen Citrobacter rodentium targets a specific subset of absorptive intestinal epithelial cells in the mid–distal colon, which stimulate T cells to produce sustained IL-22 signals to mitigate further spread of the pathogen.