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Title: | Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain | Authors: | BOGIE, Jeroen GRAJCHEN, Elien WOUTERS, Elien GARCIA CORRALES, Aida DIERCKX, Tess VANHERLE, Sam MAILLEUX, Jo GERVOIS, Pascal WOLFS, Esther Dehairs, Jonas VAN BROECKHOVEN, Jana Bowman, Andrew P. LAMBRICHTS, Ivo Gustafsson, Jan-Ake Remaley, Alan T. Mulder, Monique Swinnen, Johannes, V HAIDAR, Mansour Ellis, Shane R. Ntambi, James M. Zelcer, Noam HENDRIKS, Jerome |
Issue Date: | 2020 | Publisher: | ROCKEFELLER UNIV PRESS | Source: | JOURNAL OF EXPERIMENTAL MEDICINE, 217 (5) (Art N° e20191660) | Abstract: | Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination. | Notes: | Bogie, JFJ; Hendriks, JJA (reprint author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Diepenbeek, Belgium. Jeroen.bogie@uhasselt.be; Jerome.hendriks@uhasselt.be |
Other: | Bogie, JFJ; Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Diepenbeek, Belgium. Jeroen.bogie@uhasselt.be; Jerome.hendriks@uhasselt.be | Keywords: | Cholesterol Efflux;Myelin Phagocytosis;Fatty-Acids;Electrospray-Ionization;Stimulated Macrophages;Deficiency Protects;Gene-Expression;Foam Cells;Mice;Remyelination | Document URI: | http://hdl.handle.net/1942/31459 | ISSN: | 0022-1007 | e-ISSN: | 1540-9538 | DOI: | 10.1084/jem.20191660 | ISI #: | WOS:000531028800015 | Rights: | 2020 Bogie et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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