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Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity

Cellular & Molecular Immunology 2023年第6期20卷 666-679页

作者： Elien Grajchen Melanie Loix Paulien Baeten Beatriz F.Côrte-Real Ibrahim Hamad Sam Vanherle Mansour Haidar Jonas Dehairs Jelle Y.Broos James M.Ntambi Robert Zimmermann Rolf Breinbauer Piet Stinissen Niels Hellings Sanne G.S.Verberk Gijs Kooij Martin Giera Johannes V.Swinnen Bieke Broux markus kleinewietfeld Jerome J.A.Hendriks Jeroen F.J.Bogie Department of Immunology and Infection Biomedical Research InstituteHasselt UniversityDiepenbeekBelgium University MS Center Hasselt PeltBelgium Neuro-Immune Connections and Repair Lab Department of Immunology and InfectionBiomedical Research InstituteHasselt UniversityDiepenbeekBelgium VIB Laboratory of Translational Immunomodulation VIB Center for Inflammation ResearchHasselt UniversityDiepenbeekBelgium Department of Oncology Laboratory of Lipid Metabolism and CancerLKI–Leuven Cancer InstituteKU Leuven-University of LeuvenLeuvenBelgium Department of Molecular Cell Biology and Immunology Amsterdam University Medical CenterVrije Universiteit AmsterdamAmsterdam NeuroscienceMS Center AmsterdamAmsterdamThe Netherlands Center for Proteomics and Metabolomics Leiden University Medical CenterLeidenThe Netherlands Department of Biochemistry Department of Nutritional SciencesUniversity of Wisconsin-MadisonMadisonUSA Institute of Molecular Biosciences University of GrazGrazAustria BioTechMed-Graz GrazAustria Institute of Organic Chemistry Graz University of TechnologyGrazAustria Cardiovascular Research Institute Maastricht Department of Internal MedicineMaastricht UniversityMaastrichtThe Netherlands

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis(MS).Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and *** date,however,the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly ***,we report that stearoyl-CoA desaturase-1(SCD1),an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors,acts as an endogenous brake on regulatory T-cell(Treg)differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent *** by RNA sequencing and lipidomics analysis,we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase(ATGL).ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor *** findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity,with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.

关键词： Regulatory T cells Autoimmunity Fatty acid metabolism Stearoyl-CoA desaturase-1 Multiple sclerosis

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