Atg5 Is Essential for the Development and Survival of Innate Lymphocytes.
Atg5 Is Essential for the Development and Survival of Innate Lymphocytes.
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DOI：
10.1016/j.celrep.2016.04.082
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发表时间：
2016-05-31
期刊：
影响因子：
8.8
通讯作者：
Sun JC
中科院分区：
文献类型：
--
作者：
O'Sullivan TE;Geary CD;Weizman OE;Geiger TL;Rapp M;Dorn GW 2nd;Overholtzer M;Sun JC
自噬是一种重要的细胞生存机制，是适应性淋巴细胞发育所必需的；然而，它在先天淋巴细胞（ILC）发育中的作用仍然未知。此外，人们对稳态期间促进淋巴细胞自噬的条件知之甚少。在这里，我们证明 Atg5 是自噬机制的重要组成部分，是成熟自然杀伤 (NK) 细胞和 1、2 和 3 组先天淋巴细胞 (ILC) 发育所必需的。虽然 Atg5 的诱导性消融对于淋巴细胞缺失小鼠中淋巴细胞前体和成熟淋巴细胞的稳态是可有可无的，但我们发现，在淋巴细胞减少宿主的稳态增殖过程中，适应性淋巴细胞和先天淋巴细胞中都会诱导自噬，通过限制细胞内在的凋亡来促进其生存。稳态增殖后通过二甲双胍治疗诱导自噬通过 Atg5 依赖性机制增加淋巴细胞数量。这些发现强调了自噬在淋巴细胞减少症期间 ILC 发育和淋巴细胞存活中的重要作用。自噬是应激期间诱导的一种重要的细胞生存机制。奥沙利文等人。证明必需的自噬基因 Atg5 通过限制细胞内在的细胞凋亡，是所有 ILC 谱系的发育和生存所必需的。
Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC) development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here we demonstrate that Atg5, an essential component of the autophagy machinery, is required for the development of mature natural killer (NK) cells and group 1, 2, and 3 innate lymphoid cells (ILC). While inducible ablation of Atg5 was dispensable for the homeostasis of lymphocyte precursors and mature lymphocytes in lymphoreplete mice, we found that autophagy is induced in both adaptive and innate lymphocytes during homeostatic proliferation in lymphopenic hosts to promote their survival by limiting cell-intrinsic apoptosis. Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism. These findings highlight the essential role for autophagy in ILC development and lymphocyte survival during lymphopenia. Autophagy is an essential cellular survival mechanism induced during periods of stress. O’Sullivan et al. demonstrate that the essential autophagy gene Atg5 is required for the development and survival of all ILC lineages by limiting cell-intrinsic apoptosis.