TY - JOUR
T1 - Atg5 Is Essential for the Development and Survival of Innate Lymphocytes
AU - O'Sullivan, Timothy E.
AU - Geary, Clair D.
AU - Weizman, Orr El
AU - Geiger, Theresa L.
AU - Rapp, Moritz
AU - Dorn, Gerald W.
AU - Overholtzer, Michael
AU - Sun, Joseph C.
N1 - Funding Information:
We thank members of the J.C.S. lab for technical support, experimental assistance, insightful comments, and helpful discussions. You-Wen He, Eric Vivier, Liang Deng, and Noboru Mizushima provided mice, reagents, and expertise critical to this study. T.E.O. was supported by the American Cancer Society. M.R. was supported by a fellowship from the DAAD (Germany). T.L.G. was supported by a F31 award from the National Institute of Allergy and Infectious Diseases (AI114019). G.W.D. was supported by a grant from the NIH (HL59888). J.C.S. was supported by the Ludwig Center for Cancer Immunotherapy, the Searle Scholars Program, the Cancer Research Institute, and grants from the NIH (AI100874 and P30CA008748).
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/5/31
Y1 - 2016/5/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84971255143&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.04.082
DO - 10.1016/j.celrep.2016.04.082
M3 - Article
C2 - 27210760
AN - SCOPUS:84971255143
SN - 2211-1247
VL - 15
SP - 1910
EP - 1919
JO - Cell Reports
JF - Cell Reports
IS - 9
ER -