Regulatory T cells and effector T cells (such as those of the TH17 subset of helper T cells) have distinct metabolic requirements for their development and proliferation, with the former reliant on fatty acid oxidation and the latter reliant on glycolysis. In Nature Medicine, Sparwasser and colleagues describe a soil bacterium–derived compound, SorA, that skews the development of both human T cells and mouse T cells toward regulatory T cells at the expense of TH17 cells. SorA inhibits ACC1, an enzyme involved in fatty acid metabolism, by blocking its phosphorylation. TH17 cells from mice with conditional deletion of the gene encoding ACC1 or treated with SorA show impaired glycolysis and glutaminolysis. Accordingly, mice with conditional deletion or treated with an inhibitor show greatly ameliorated experimental autoimmune encephalitis. SorA is therefore an effective anti-glycolytic drug, and targeting ACC1 may represent a fruitful strategy for controlling autoinflammatory and autoimmune diseases.

Nat. Med. (5 October 2014) doi:10.1038/nm.3704