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

• 成果类型: Article
• 署名作者: 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.
• 署名单位: University of Alabama System; University of Alabama Birmingham; University of Alabama System; University of Alabama Birmingham
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6503
• DOI: 10.1038/s41586-024-07288-1
• 发表日期: 2024-05-16
• 页码: 669-+
• 关键词: serum amyloid-a; citrobacter-rodentium; interleukin 22; host-defense; mice; identification; expression; infection; immunity; protein

摘要

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.