| Autor: |
Araujo, Leandro P., Edwards, Madeline, Irie, Koichiro, Huang, Yiming, Kawano, Yoshinaga, Tran, Alexander, De Michele, Simona, Bhagat, Govind, Wang, Harris H., Ivanov, Ivaylo I. |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 98, p1-16, 16p |
| Abstrakt: |
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 (TH17) cells, and secondary lymphoid organs. ILC3s were dispensable for generation of TH17 and TH22 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 TH17 cell functions. Editor's summary: Group 3 innate lymphoid cells (ILC3s) contribute to intestinal homeostasis and immunity against gut pathogens. Distinguishing the functions of ILC3s from those of T helper 17 (TH17) cells has remained challenging because of similar transcription factor dependencies and cytokine production profiles. To better define ILC3-specific roles, Araujo et al. developed genetically engineered mice that lack ILC3s while retaining endogenous T cells and secondary lymphoid organs. ILC3s were the primary producers of IL-22, which was required for the maintenance of intestinal epithelial cell homeostasis. Whereas TH17 cells were sufficient to protect against low-dose Citrobacter rodentium infection, ILC3s provided early protection and were required for survival after high-dose infection. Together, these findings identify nonredundant functions of ILC3s in mucosal homeostasis and immunity. —Claire Olingy [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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