Reviewing the impact of lipid synthetic flux on Th17 function

• Published in: Current opinion in immunology 2017-06, Vol.46, p.121-126
• Main Authors: Kidani, Yoko, Bensinger, Steven J
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - immunology; Cholesterol - metabolism; Disease Susceptibility; Fatty Acids - biosynthesis; Humans; Immunomodulation; Lipid Metabolism; Lipids - biosynthesis; Lymphocyte Activation - immunology; Metabolic Networks and Pathways; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2017.03.012

•Discuss the fundamentals of the cholesterol and fatty acid synthetic pathways.•Metabolic fluxes through cholesterogenic and lipogenic pathways regulate RORγ activity.•Lipogenic pathways impact the balance of Th17/Treg. CD4+ T helper 17 cells (Th17) acquire specific effector functions in response to activation and instructional signals. Accumulating evidence indicates that specific cellular lipid metabolic pathways play essential roles in regulating the differentiation and function of Th17 cells. Mechanistic studies reveal that metabolic fluxes through both the cholesterol and long chain fatty acid biosynthetic pathways are important in controlling RORγ transcriptional activity through their ability to generate lipid ligands of RORγ. Genetic and pharmacologic studies demonstrate that altering the flux through these lipid biosynthetic pathways impacts the generation of IL-17 as well as the balance of Th17 and CD4+ regulatory T cells (Tregs). In this mini-review, we briefly introduce the mechanics of cholesterol and long chain fatty acid biosynthesis. We also discuss the evidence underlying the unique role that these lipid metabolic pathways play in intrinsically regulating the fate and function of Th17 cells under normal and pathogenic conditions.