Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY 10032, USA.
Sci Immunol. 2024 Aug 16;9(98):eade7530. doi: 10.1126/sciimmunol.ade7530.
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 (T17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of T17 and T22 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 . 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 T17 cell functions.
3 组先天淋巴细胞（ILC3）如何在存在 T 细胞的情况下调节黏膜保护作用仍知之甚少。在这里，我们使用维持内源性 T 细胞、辅助性 T 细胞 17（T17）细胞和次级淋巴器官的 ILC3 缺陷小鼠来检查 ILC3 在肠道免疫中的功能。ILC3 对于对共生菌和致病菌的 T17 和 T22 细胞反应的产生是可有可无的，并且在感染之前或期间，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，但 ILC3 和 ILC3 衍生的 IL-22 对于维持肠道上皮的稳态功能是必需的。在 T 细胞充足、ILC3 缺陷的小鼠中，能够清除病原体并在低剂量的 感染后存活。然而，ILC3 通过激活组织保护性免疫途径在感染的早期时间点促进病原体耐受。因此，ILC3 在高剂量感染后是存活所必需的。我们的结果表明，ILC3 在免疫充足的动物中具有依赖于背景的作用，并为 ILC3 和 T17 细胞功能的解耦提供了蓝图。
