美国阿拉巴马大学Casey T. Weaver和Carlene L. Zindl共同合作，近期取得重要工作进展。他们研究提出，鼠柠檬酸杆菌（ Citrobacter rodentium，Cr）靶向远端结肠细胞募集T细胞有助于屏障防御。相关研究成果2024年4月10日在线发表于《自然》杂志上。

据介绍，白细胞介素22（IL-22）在肠道屏障的免疫防御中具有非冗余作用。T细胞，而不是先天性淋巴细胞，在维持IL-22信号传导方面发挥着不可或缺的作用，IL-22信号是在肠道病原体牛仔柠檬酸杆菌（Cr）感染期间保护结肠隐窝免受侵袭所必需的。然而，T细胞来源的IL-22靶向的肠上皮细胞（IEC）亚群，以及T细胞来源的IL-22如何在IEC中维持激活，仍不明确。

研究人员确定了中远端结肠中的吸收IEC的一个细胞亚群，这些IEC是Cr特异性靶向的，并且对IL-22信号传导有不同的反应。这些结肠细胞表达主要组织相容性复合体II类（MHCII）是从Cr特异性T细胞引发持续的IL-22信号传导所必需的，这是抑制Cr侵袭所必需的。

总之，这一研究结果解释了宿主对Cr反应区域化的基础，并证明上皮细胞必须从产生IL-22的T细胞中获得MHCII依赖性帮助，以协调肠道中的免疫保护。

附：英文原文

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

Author: 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.

Issue&Volume: 2024-04-10

Abstract: Interleukin 22 (IL-22) has a non-redundant role in immune defence of the intestinal barrier1,2,3. 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.

DOI: 10.1038/s41586-024-07288-1

Source: https://www.nature.com/articles/s41586-024-07288-1