New insights into the metabolism of Th17 cells

Abstract

T helper 17 (Th17) cells are IL-17-producing CD4 T cells that play a crucial role in autoimmune diseases. IL-17 is a key cytokine for host protection against mucosal and skin infection but is also one of the major pathogenic cytokines. IL-1 and IL-23 are requisite for stimulating pathogenic Th17 cell differentiation and proliferation. Therapeutics targeting the IL-17/IL-23 pathway are widely used clinically for the treatment of autoimmune diseases. Besides IL-17, pathogenic Th17 cells produce granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, interferon γ, IL-21 and IL-22. However, Th17-targeted therapy has not yet been established. T cell metabolism orchestrates T cell survival, cell differentiation, epigenetic change and function and each T cell subset favors a particular metabolic pathway. Recent studies have provided novel insights into the role of T cell metabolism in the pathogenesis of autoimmune diseases. The current review focuses on the role of Th17 cell metabolism in autoimmune diseases, particularly glycolysis, amino acid metabolism, lipid metabolism, as well as the regulators of these processes, including mTORC1. Therapeutics targeting T cell metabolism in autoimmune diseases could serve as a possible treatment option for patients who are refractory to or unresponsive to conventional therapy.