Bcl-2 supports survival and metabolic fitness of quiescent tissue-resident ILC3

James King, Felipe Melo Gonzalez, Bert Malengier-Devlies, Roser Tachó Piñot, Marlène S. Magalhaes, Suzanne Hodge, Xavier Romero Ros, Rebecca Gentek, Matthew Hepworth

Research output: Contribution to journalArticlepeer-review

Abstract

Group 3 innate lymphoid cells (ILC3) are potent effector cells with critical roles in enforcing immunity, barrier integrity and tissue homeostasis along the gastrointestinal tract. ILC3 are considered primarily tissue-resident cells, seeding the gastrointestinal tract during embryonic stages and early life. However, the mechanisms through which mature ILC3 are maintained within adult tissues are poorly understood. Here, we report that LTi-like ILC3 exhibit minimal turnover in the healthy adult intestinal tract, persist for extended periods of time, and display a quiescent phenotype. Strikingly, during enteric bacterial infection LTi-like ILC3 also exhibit negligible hematopoietic replenishment and remain non-proliferative, despite robustly producing cytokines. Survival of LTi-like ILC3 was found to be dependent upon the balance of the metabolic activity required to drive effector function and anti-apoptotic programs. Notably, the pro-survival protein Bcl-2 was required for the survival of LTi-like ILC3 ex vivo but was rendered partially dispensable if mitochondrial respiration was inhibited. Together we demonstrate LTi-like ILC3 are a tissue-resident, quiescent population that persist independently of haematopoietic replenishment to survive within the intestinal microenvironment.
Original languageEnglish
JournalMucosal Immunology
Publication statusPublished - 2023

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