Lipid metabolism in Th17 cell function

Among the subset of T helper cells, Th17 cells are known to play a crucial role in the pathogenesis of various autoimmune disorders, such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. The master transcription factor retinoid-related orphan receptor gamma t (ROR?t), a nuclear hormone receptor, plays a vital role in inducing Th17-cell differentiation. Recent findings suggest that metabolic control is critical for Th17-cell differentiation, particularly through the engagement of de novo lipid biosynthesis. Inhibition of lipid biosynthesis, either through the use of pharmacological inhibitors or by the deficiency of related enzymes in CD4(+) T cells, results in significant suppression of Th17-cell differentiation. Mechanistic studies indicate that metabolic fluxes through both the fatty acid and cholesterol biosynthetic path-ways are essential for controlling ROR?t activity through the generation of a lipid ligand of ROR gamma t. This review highlights recent findings that underscore the significant role of lipid metabolism in the differentiation and func-tion of Th17 cells, as well as elucidating the distinctive molecular pathways that drive the activation of ROR gamma t by cellular lipid metabolism. We further elaborate on a pioneering therapeutic approach for ameliorating autoim-mune disorders via the inhibition of ROR gamma t.(c) 2023 Elsevier Inc. All rights reserved.