The cIAP ubiquitin ligases sustain type 3 γδ T cells and ILC during aging to promote barrier immunity.
J Exp Med
; 220(8)2023 08 07.
Article
en En
| MEDLINE
| ID: mdl-37440178
ABSTRACT
Early-life cues shape the immune system during adulthood. However, early-life signaling pathways and their temporal functions are not well understood. Herein, we demonstrate that the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2), which are E3 ubiquitin ligases, sustain interleukin (IL)-17-producing γ δ T cells (γδT17) and group 3 innate lymphoid cells (ILC3) during late neonatal and prepubescent life. We show that cell-intrinsic deficiency of cIAP1/2 at 3-4 wk of life leads to downregulation of the transcription factors cMAF and RORγt and failure to enter the cell cycle, followed by progressive loss of γδT17 cells and ILC3 during aging. Mice deficient in cIAP1/2 have severely reduced γδT17 cells and ILC3, present with suboptimal γδT17 responses in the skin, lack intestinal isolated lymphoid follicles, and cannot control intestinal bacterial infection. Mechanistically, these effects appear to be dependent on overt activation of the non-canonical NF-κB pathway. Our data identify cIAP1/2 as early-life molecular switches that establish effective type 3 immunity during aging.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ubiquitina
/
Inmunidad Innata
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Exp Med
Año:
2023
Tipo del documento:
Article