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

• Published in: Science immunology Vol. 9; no. 98; p. eade7530
• Main Authors: Araujo, Leandro P, Edwards, Madeline, Irie, Koichiro, Huang, Yiming, Kawano, Yoshinaga, Tran, Alexander, De Michele, Simona, Bhagat, Govind, Wang, Harris H, Ivanov, Ivaylo I
• Format: Journal Article
• Language: English
• Published: United States 16.08.2024
• Subjects: Animals; Citrobacter rodentium - immunology; Enterobacteriaceae Infections - immunology; Immunity, Innate - immunology; Immunity, Mucosal - immunology; Interleukin-22; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Lymphocytes - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Th17 Cells - immunology
• ISSN: 2470-9468
• 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 (T 17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of T 17 and T 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 . 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 17 cell functions.