Bcl-2 supports survival and metabolic fitness of quiescent tissue-resident ILC3.
Bcl-2 supports survival and metabolic fitness of quiescent tissue-resident ILC3.
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DOI：
10.1016/j.mucimm.2023.07.001
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发表时间：
2023-10
影响因子：
8
通讯作者：
Hepworth, Matthew R.
中科院分区：
文献类型：
--
作者：
King, James I.;Melo-Gonzalez, Felipe;Malengier-Devlies, Bert;Tacho-Pinot, Roser;Magalhaes, Marlene S.;Hodge, Suzanne H.;Ros, Xavier Romero;Gentek, Rebecca;Hepworth, Matthew R.
第3组先天性淋巴样细胞（ILC 3）是有效的效应细胞，在沿胃肠道的免疫、屏障完整性和组织稳态沿着中具有关键作用。ILC 3被认为主要是组织驻留细胞，在胚胎阶段和生命早期接种胃肠道。然而，成熟ILC 3在成体组织中维持的机制知之甚少。在这里，我们报告淋巴组织诱导剂样（LTi样）ILC 3在健康成人肠道中表现出最小的营业额，持续时间延长，并显示出静止表型。引人注目的是，在肠道细菌感染期间，LTi样ILC 3也表现出可忽略不计的造血补充，并且保持非增殖性，尽管强烈地产生细胞因子。发现LTi样ILC 3的存活依赖于驱动效应子功能所需的代谢活性与抗凋亡程序之间的平衡。值得注意的是，促存活蛋白B细胞淋巴瘤-2（Bcl-2）是LTi样ILC 3离体存活所需的，但如果线粒体呼吸被抑制，则会部分丧失。我们一起证明LTi样ILC 3是一种组织驻留的静止群体，其独立于造血补充而在肠道微环境中存活。
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 lymphoid tissue-inducer-like (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 between the metabolic activity required to drive effector function and anti-apoptotic programs. Notably, the pro-survival protein B-cell lymphoma-2 (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 hematopoietic replenishment to survive within the intestinal microenvironment.
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