Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function Journal Article


Authors: Sheppard, S.; Santosa, E. K.; Lau, C. M.; Violante, S.; Giovanelli, P.; Kim, H.; Cross, J. R.; Li, M. O.; Sun, J. C.
Article Title: Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
Abstract: Natural killer (NK) cells are cytotoxic lymphocytes capable of rapid cytotoxicity, cytokine secretion, and clonal expansion. To sustain such energetically demanding processes, NK cells must increase their metabolic capacity upon activation. However, little is known about the metabolic requirements specific to NK cells in vivo. To gain greater insight, we investigated the role of aerobic glycolysis in NK cell function and demonstrate that their glycolytic rate increases rapidly following viral infection and inflammation, prior to that of CD8+ T cells. NK cell-specific deletion of lactate dehydrogenase A (LDHA) reveals that activated NK cells rely on this enzyme for both effector function and clonal proliferation, with the latter being shared with T cells. As a result, LDHA-deficient NK cells are defective in their anti-viral and anti-tumor protection. These findings suggest that aerobic glycolysis is a hallmark of NK cell activation that is key to their function. © 2021 The Author(s)
Keywords: metabolism; glycolysis; natural killer cells; tumor surveillance; cd8+ t cells; lactate dehydrogenase a; mcmv; b16-f10; clonal proliferation; ly49h
Journal Title: Cell Reports
Volume: 35
Issue: 9
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2021-06-01
Start Page: 109210
Language: English
DOI: 10.1016/j.celrep.2021.109210
PROVIDER: scopus
PMCID: PMC8221253
PUBMED: 34077737
DOI/URL:
Notes: Article -- Export Date: 1 July 2021 -- Source: Scopus
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MSK Authors
  1. Joseph C Sun
    100 Sun
  2. Ming Li
    90 Li
  3. Justin Robert Cross
    77 Cross
  4. Colleen M Lau
    19 Lau
  5. Hyunu Kim
    1 Kim