@article{ccfdbc61d050457fb4e0b713063d44b6,
title = "Reliance on Cox10 and oxidative metabolism for antigen-specific NK cell expansion",
abstract = "Natural killer (NK) cell effector functions are dependent on metabolic regulation of cellular function; however, less is known about in vivo metabolic pathways required for NK cell antiviral function. Mice with an inducible NK-specific deletion of Cox10, which encodes a component of electron transport chain complex IV, were generated to investigate the role of oxidative phosphorylation in NK cells during murine cytomegalovirus (MCMV) infection. Ncr1-Cox10Δ/Δ mice had normal numbers of NK cells but impaired expansion of antigen-specific Ly49H+ NK cells and impaired NK cell memory formation. Proliferation in vitro and homeostatic expansion were intact, indicating a specific metabolic requirement for antigen-driven proliferation. Cox10-deficient NK cells upregulated glycolysis, associated with increased AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) activation, although this was insufficient to protect the host. These data demonstrate that oxidative metabolism is required for NK cell antiviral responses in vivo.",
keywords = "Cox10, NK cells, metabolism, murine cytomegalovirus, oxidative phosphorylation, proliferation",
author = "Mah-Som, {Annelise Y.} and Keppel, {Molly P.} and Tobin, {Joshua M.} and Ana Kolicheski and Nermina Saucier and Veronika Sexl and French, {Anthony R.} and Wagner, {Julia A.} and Fehniger, {Todd A.} and Cooper, {Megan A.}",
note = "Funding Information: This work was supported by NIH grant R01AI127752 (to M.A.C.); the Children's Discovery Institute (M.A.C.); the Rheumatology Research Foundation (to M.A.C.); NIH grants F30AI129110 (to A.Y.M.-S.), T32GM007200 (to A.Y.M.-S. and J.M.T.), R01AI078994 (to A.R.F.), and R01 CA205239 and P50CA171963 (to T.A.F.); and by Austrian Science Foundation (FWF) grant P28571 (to V.S.). We thank the Genome Technology Access Center and McDonnell Genome Institute Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center support grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. We thank the Tissue Culture Support Center at Washington University in St. Louis for technical assistance. This work used data and tools assembled by the ImmGen Consortium and Metascape, and programming support from the Satija lab. Conceptualization, A.Y.M.-S. and M.A.C.; methodology, A.Y.M.-S. M.P.K. J.M.T. J.A.W. T.A.F. and M.A.C.; investigation, A.K. A.Y.M.-S. M.P.K. J.M.T. and N.S.; software, A.K. resources, V.S. A.R.F. J.A.W. and T.A.F.; writing, A.Y.M.-S. J.M.T. M.P.K. A.K. and M.A.C. Supervision, M.A.C. The authors declare no competing interests. Funding Information: This work was supported by NIH grant R01AI127752 (to M.A.C.); the Children's Discovery Institute (M.A.C.); the Rheumatology Research Foundation (to M.A.C.); NIH grants F30AI129110 (to A.Y.M.-S.), T32GM007200 (to A.Y.M.-S. and J.M.T.), R01AI078994 (to A.R.F.), and R01 CA205239 and P50CA171963 (to T.A.F.); and by Austrian Science Foundation (FWF) grant P28571 (to V.S.). We thank the Genome Technology Access Center and McDonnell Genome Institute Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center support grant P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. We thank the Tissue Culture Support Center at Washington University in St. Louis for technical assistance. This work used data and tools assembled by the ImmGen Consortium and Metascape, and programming support from the Satija lab. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jun,
day = "1",
doi = "10.1016/j.celrep.2021.109209",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
number = "9",
}