Context-dependent role of group 3 innate lymphoid cells in mucosal protection

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2024-08-16 DOI:10.1126/sciimmunol.ade7530

Leandro P. Araujo, Madeline Edwards, Koichiro Irie, Yiming Huang, Yoshinaga Kawano, Alexander Tran, Simona De Michele, Govind Bhagat, Harris H. Wang, Ivaylo I. Ivanov

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引用次数: 0

Abstract

How group 3 innate lymphoid cells (ILC3s) regulate mucosal protection in the presence of T cells remains poorly understood. Here, we examined ILC3 function in intestinal immunity using ILC3-deficient mice that maintain endogenous T cells, T helper 17 (T_H17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of T_H17 and T_H22 cell responses to commensal and pathogenic bacteria, and absence of ILC3s did not affect IL-22 production by CD4 T cells before or during infection. However, despite the presence of IL-22–producing T cells, ILC3s and ILC3-derived IL-22 were required for maintaining homeostatic functions of the intestinal epithelium. T cell–sufficient, ILC3-deficient mice were capable of pathogen clearance and survived infection with a low dose of Citrobacter rodentium. However, ILC3s promoted pathogen tolerance at early time points of infection by activating tissue-protective immune pathways. Consequently, ILC3s were indispensable for survival after high-dose infection. Our results demonstrate a context-dependent role for ILC3s in immune-sufficient animals and provide a blueprint for uncoupling of ILC3 and T_H17 cell functions.

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第 3 组先天性淋巴细胞在粘膜保护中的作用与环境有关。

人们对第3群先天性淋巴细胞（ILC3）如何在存在T细胞的情况下调节粘膜保护功能仍知之甚少。在这里，我们利用保持内源性T细胞、T辅助17（TH17）细胞和次级淋巴器官的ILC3缺陷小鼠研究了ILC3在肠道免疫中的功能。ILC3对于产生TH17和TH22细胞对共生细菌和致病细菌的反应是不可或缺的，而且在感染前或感染期间，ILC3的缺失并不影响CD4 T细胞产生IL-22。然而，尽管存在产生 IL-22 的 T 细胞，ILC3s 和 ILC3 衍生的 IL-22 仍是维持肠上皮细胞平衡功能所必需的。T细胞充足、ILC3缺乏的小鼠能够清除病原体，并在感染低剂量的柠檬杆菌后存活下来。然而，ILC3 通过激活组织保护性免疫途径，在感染早期促进病原体耐受。因此，ILC3s 是高剂量感染后存活所不可或缺的。我们的研究结果证明了 ILC3s 在免疫功能低下动物中的作用与环境有关，并为 ILC3 和 TH17 细胞功能的解耦提供了蓝图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.