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Atg5 Is Essential for the Development and Survival of Innate Lymphocytes.

Abstract：

: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 ILCs. Although 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

O'Sullivan TE,Geary CD,Weizman OE,Geiger TL,Rapp M,Dorn GW 2nd,Overholtzer M,Sun JC

doi

10.1016/j.celrep.2016.04.082

subject

Has Abstract

pub_date

2016-05-31 00:00:00

pages

1910-9

issue

9

issn

2211-1247

pii

S2211-1247(16)30527-7

journal_volume

15

pub_type

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