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

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外文摘要：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 autoimmunity.To date,however,the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood.Here,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 manner.Guided 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 gamma.Our 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.

外文关键词：

Regulatory T cellsAutoimmunityFatty acid metabolismStearoyl-CoA desaturase-1Multiple sclerosis

作者：

Elien Grajchen、Melanie Loix、Paulien Baeten、Beatriz F.C?rte-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

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作者单位：

Department of Immunology and Infection,Biomedical Research Institute,Hasselt University,Diepenbeek,Belgium

University MS Center Hasselt,Pelt,Belgium

Neuro-Immune Connections and Repair Lab,Department of Immunology and Infection,Biomedical Research Institute,Hasselt University,Diepenbeek,Belgium

VIB Laboratory of Translational Immunomodulation,VIB Center for Inflammation Research,Hasselt University,Diepenbeek,Belgium

Department of Oncology,Laboratory of Lipid Metabolism and Cancer,LKI-Leuven Cancer Institute,KU Leuven-University of Leuven,Leuven,Belgium

Department of Molecular Cell Biology and Immunology,Amsterdam University Medical Center,Vrije Universiteit Amsterdam,Amsterdam Neuroscience,MS Center Amsterdam,Amsterdam,The Netherlands

Center for Proteomics and Metabolomics,Leiden University Medical Center,Leiden,The Netherlands

Department of Biochemistry,Department of Nutritional Sciences,University of Wisconsin-Madison,Madison,USA

Institute of Molecular Biosciences,University of Graz,Graz,Austria

BioTechMed-Graz,Graz,Austria

Institute of Organic Chemistry,Graz University of Technology,Graz,Austria

Cardiovascular Research Institute Maastricht,Department of Internal Medicine,Maastricht University,Maastricht,The Netherlands

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基金：

Flemish Fund for Scientific Research(FWO Vlaanderen)Flemish Fund for Scientific Research(FWO Vlaanderen)Flemish Fund for Scientific Research(FWO Vlaanderen)Flemish Fund for Scientific Research(FWO Vlaanderen)Flemish Fund for Scientific Research(FWO Vlaanderen)Belgian Charcot FoundationBelgian Charcot FoundationBelgian Charcot FoundationInterreg V-A EMR programInterreg V-A EMR programspecial research fund UHasselt(BOF)a National Institutes of Health GrantEuropean Research Council(ERC)under the European Union's Horizon 2020 research and innovation programa SALK grant from the government of Flandersan Odysseus grant of the Research Foundation Flanders,Belgium(FWO)

项目编号：

12J9116N12JG119N12U7718N1S15519NG099618NFCS-2016-EG7R-8676R-6832EURLIPIDSEMR23R01 DK062388640116

出版年：

2023

DOI：

10.1038/s41423-023-01011-2

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(6)

参考文献量83