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

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 s...

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Autores principales: Sheppard, Sam, Santosa, Endi K., Lau, Colleen M., Violante, Sara, Giovanelli, Paolo, Kim, Hyunu, Cross, Justin R., Li, Ming O., Sun, Joseph C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221253/
https://www.ncbi.nlm.nih.gov/pubmed/34077737
http://dx.doi.org/10.1016/j.celrep.2021.109210
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author Sheppard, Sam
Santosa, Endi K.
Lau, Colleen M.
Violante, Sara
Giovanelli, Paolo
Kim, Hyunu
Cross, Justin R.
Li, Ming O.
Sun, Joseph C.
author_facet Sheppard, Sam
Santosa, Endi K.
Lau, Colleen M.
Violante, Sara
Giovanelli, Paolo
Kim, Hyunu
Cross, Justin R.
Li, Ming O.
Sun, Joseph C.
author_sort Sheppard, Sam
collection PubMed
description 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.
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spelling pubmed-82212532021-06-23 Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function Sheppard, Sam Santosa, Endi K. Lau, Colleen M. Violante, Sara Giovanelli, Paolo Kim, Hyunu Cross, Justin R. Li, Ming O. Sun, Joseph C. Cell Rep Article 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. 2021-06-01 /pmc/articles/PMC8221253/ /pubmed/34077737 http://dx.doi.org/10.1016/j.celrep.2021.109210 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Sheppard, Sam
Santosa, Endi K.
Lau, Colleen M.
Violante, Sara
Giovanelli, Paolo
Kim, Hyunu
Cross, Justin R.
Li, Ming O.
Sun, Joseph C.
Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
title Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
title_full Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
title_fullStr Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
title_full_unstemmed Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
title_short Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
title_sort lactate dehydrogenase a-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221253/
https://www.ncbi.nlm.nih.gov/pubmed/34077737
http://dx.doi.org/10.1016/j.celrep.2021.109210
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