Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain
| Autor: | Jan-Åke Gustafsson, Ivo Lambrichts, Elien Wouters, Jeroen F. J. Bogie, Aida Garcia Corrales, Pascal Gervois, Noam Zelcer, Esther Wolfs, Jo Mailleux, Alan T. Remaley, Tess Dierckx, Jana Van Broeckhoven, Shane R. Ellis, Jerome J. A. Hendriks, Johannes V. Swinnen, Monique T. Mulder, Jonas Dehairs, James M. Ntambi, Sam Vanherle, Andrew P. Bowman, Elien Grajchen, Mansour Haidar |
|---|---|
| Přispěvatelé: | Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Internal Medicine, Imaging Mass Spectrometry (IMS), RS: M4I - Imaging Mass Spectrometry (IMS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
ELECTROSPRAY-IONIZATION CHOLESTEROL EFFLUX Phagocyte FOAM CELLS REMYELINATION Myelin 0302 clinical medicine Neuroinflammation MYELIN PHAGOCYTOSIS Immunology and Allergy Myelin Sheath GENE-EXPRESSION Phagocytes biology Microglia Chemistry Fatty Acids Brain DEFICIENCY PROTECTS Endocytosis Cell biology Protein Kinase C-delta Cholesterol Phenotype medicine.anatomical_structure lipids (amino acids peptides and proteins) FATTY-ACIDS Stearoyl-CoA Desaturase Intracellular ATP Binding Cassette Transporter 1 Innate Immunity and Inflammation Immunology Article Cell Line 03 medical and health sciences medicine Animals Humans STIMULATED MACROPHAGES Remyelination Inflammation Macrophages MICE Metabolism 030104 developmental biology ABCA1 biology.protein Stearoyl-CoA desaturase-1 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | Journal of experimental medicine, 217(5):e20191660. Rockefeller University Press Journal of Experimental Medicine, 217(5):e20191660. Rockefeller University Press Journal of Experimental Medicine, 217(5):20191660. Rockefeller University Press The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | In this study, Bogie, Grajchen et al. show that monounsaturated fatty acids formed by stearoyl-CoA desaturase-1 impair the reparative features of macrophages and microglia in demyelinating disorders by reducing their lipid efflux capacity. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|