T cells undergo metabolic reprogramming during differentiation, but the mechanistic basis of these changes is incompletely understood. In the Journal of Clinical Investigation, Rathmell and colleagues examine the metabolic requirements of effector cells (the TH1 and TH17 subsets of helper T cells) and regulatory T cells (Treg cells) in vitro and in vivo. TH1 and TH17 cells rely on glycolysis, whereas Treg cells have low glycolytic capacity and use mitochondrial and fatty acid oxidation. Metabolomic analysis identifies the kinase PDHK1 as serving a key role in metabolic control of the function and survival of specifically TH17 cells and Treg cells but not TH1 cells, with high, intermediate and low expression of PDHK1, respectively, by these cells. Blockade of PDHK1 in mouse models of inflammatory bowel disease or experimental allergic encephalitis both increases the number of Treg cells and diminishes that of TH17 cells in vivo. PDHK1 therefore sits at a key signaling juncture that controls the glycolytic and oxidative metabolism of T cells.

J. Clin. Invest. (1 December 2014) doi:10.1172/JCI76012