Please use this identifier to cite or link to this item:
Title: S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate
Authors: Tyrakis P.A.
Palazon A.
Macias D.
Lee K.L. 
Phan A.T.
Veliça P.
You J.
Chia G.S.
Sim J.
Doedens A.
Abelanet A.
Evans C.E.
Griffiths J.R.
Poellinger L. 
Goldrath A.W.
Johnson R.S.
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Tyrakis P.A., Palazon A., Macias D., Lee K.L., Phan A.T., Veliça P., You J., Chia G.S., Sim J., Doedens A., Abelanet A., Evans C.E., Griffiths J.R., Poellinger L., Goldrath A.W., Johnson R.S. (2016). S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature 540 (7632) : 236-241. ScholarBank@NUS Repository.
Abstract: R-2-hydroxyglutarate accumulates to millimolar levels in cancer cells with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both metabolite enantiomers, R- and S-2-hydroxyglutarate, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that 2-hydroxyglutarate accumulates in mouse CD8+ T cells in response to T-cell receptor triggering, and accumulates to millimolar levels in physiological oxygen conditions through a hypoxia-inducible factor 1-alpha (HIF-1α)-dependent mechanism. S-2-hydroxyglutarate predominates over R-2-hydroxyglutarate in activated T cells, and we demonstrate alterations in markers of CD8+ T-cell differentiation in response to this metabolite. Modulation of histone and DNA demethylation, as well as HIF-1α stability, mediate these effects. S-2-hydroxyglutarate treatment greatly enhances the in vivo proliferation, persistence and anti-tumour capacity of adoptively transferred CD8+ T cells. Thus, S-2-hydroxyglutarate acts as an immunometabolite that links environmental context, through a metabolic-epigenetic axis, to immune fate and function. ? 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Source Title: Nature
ISSN: 280836
DOI: 10.1038/nature20165
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Aug 13, 2020

Page view(s)

checked on Aug 13, 2020

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.