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 H 17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of T H 17 and T H 22 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 H 17 cell functions.

中文翻译：

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第 3 组先天淋巴细胞在粘膜保护中的环境依赖性作用


在 T 细胞存在的情况下，第 3 组先天淋巴细胞 （ILC3） 如何调节粘膜保护仍然知之甚少。在这里，我们使用维持内源性 T 细胞、辅助性 T 细胞 17 （T H 17） 细胞和次级淋巴器官的 ILC3 缺陷小鼠检查了 ILC3 在肠道免疫中的功能。ILC3 对于产生 T H 17 和 T H 22 细胞对共生菌和病原菌的反应是可有可无的，并且 ILC3 的缺失不会影响 CD4 T 细胞在感染前或感染期间产生 IL-22。然而，尽管存在产生 IL-22 的 T 细胞，但维持肠上皮的稳态功能需要 ILC3 和 ILC3 衍生的 IL-22。T 细胞充足、ILC3 缺陷的小鼠能够清除病原体，并在使用低剂量的啮齿柠檬酸杆菌感染后存活下来。然而，ILC3s 通过激活组织保护性免疫通路促进感染早期的病原体耐受性。因此，ILC3 对于大剂量感染后的生存是必不可少的。我们的结果表明 ILC3s 在免疫力充足的动物中具有上下文依赖性作用，并为 ILC3 和 T H 17 细胞功能的解偶联提供了蓝图。