The metabolic needs of migrating Tregs

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Science  08 Dec 2017:
Vol. 358, Issue 6368, pp. 1267-1268
DOI: 10.1126/science.358.6368.1267-e

Regulatory T cells (Tregs) are thought to rely primarily on oxidative metabolism, in contrast to CD4+ T helper subsets (TH1, TH2, and TH17 cells), which are highly glycolytic. However, Kishore et al. find that integrins (LFA-1) and costimulatory molecules (CD28) can enhance Treg glycolysis, whereas the coinhibitory receptor CTLA-4 can block it. Glycolysis is required for Treg migration and depends on the enzyme glucokinase, which is induced by the PI3K-mTORC2 signaling pathway. Tregs lacking elements of this pathway are unable to migrate effectively to sites of inflammation. Likewise, Tregs from patients with a polymorphism endowing increased glucokinase activity showed enhanced chemokine-induced motility. This work opens the possibility of targeting specific glycolytic enzymes to selectively manipulate the migration of different T cell subsets.

Immunity 47, 875–889 (2017).

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