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Title: | Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity | Authors: | GRAJCHEN, Elien LOIX, Melanie BAETEN, Paulien FERNANDES CORTE-REAL, Beatriz HAMAD, Ibrahim VANHERLE, Sam HAIDAR, Mansour Dehairs, Jonas Broos, Jelle Y. Ntambi, James M. Zimmermann, Robert Breinbauer, Rolf STINISSEN, Piet HELLINGS, Niels Verberk, Sanne G. S. Kooij, Gijs Giera, Martin Swinnen, Johannes V. BROUX, Bieke KLEINEWIETFELD, Markus HENDRIKS, Jerome BOGIE, Jeroen |
Issue Date: | 2023 | Publisher: | CHIN SOCIETY IMMUNOLOGY | Source: | Cellular & Molecular Immunology, 20 (6) , p. 666 -679 | Abstract: | 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. | Notes: | Bogie, JFJ (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Diepenbeek, Belgium.; Bogie, JFJ (corresponding author), Univ MS Ctr Hasselt, Pelt, Belgium. jeroen.bogie@uhasselt.be |
Keywords: | Regulatory T cells;Autoimmunity;Fatty acid metabolism;Stearoyl-CoA desaturase-1;Multiple sclerosis | Document URI: | http://hdl.handle.net/1942/40271 | ISSN: | 1672-7681 | e-ISSN: | 2042-0226 | DOI: | 10.1038/s41423-023-01011-2 | ISI #: | 000967184600001 | Rights: | The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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