Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis.

Autor: Falcão AM; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden. ana.mendanha.falcao@ki.se., van Bruggen D; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden., Marques S; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden., Meijer M; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden., Jäkel S; MRC Centre for Regenerative Medicine and MS Society Edinburgh Centre, Edinburgh bioQuarter, University of Edinburgh, Edinburgh, UK., Agirre E; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden., Samudyata; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden., Floriddia EM; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden., Vanichkina DP; Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, New South Wales , Australia.; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia., Ffrench-Constant C; MRC Centre for Regenerative Medicine and MS Society Edinburgh Centre, Edinburgh bioQuarter, University of Edinburgh, Edinburgh, UK., Williams A; MRC Centre for Regenerative Medicine and MS Society Edinburgh Centre, Edinburgh bioQuarter, University of Edinburgh, Edinburgh, UK., Guerreiro-Cacais AO; Department of Clinical Neuroscience (CNS), Karolinska Institutet, CMM, Stockholm, Sweden., Castelo-Branco G; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, Stockholm, Sweden. goncalo.castelo-branco@ki.se.; Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, Stockholm, Sweden. goncalo.castelo-branco@ki.se.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2018 Dec; Vol. 24 (12), pp. 1837-1844. Date of Electronic Publication: 2018 Nov 12.
DOI: 10.1038/s41591-018-0236-y
Abstrakt: Multiple sclerosis (MS) is characterized by an immune system attack targeting myelin, which is produced by oligodendrocytes (OLs). We performed single-cell transcriptomic analysis of OL lineage cells from the spinal cord of mice induced with experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of MS. We found unique OLs and OL precursor cells (OPCs) in EAE and uncovered several genes specifically alternatively spliced in these cells. Surprisingly, EAE-specific OL lineage populations expressed genes involved in antigen processing and presentation via major histocompatibility complex class I and II (MHC-I and -II), and in immunoprotection, suggesting alternative functions of these cells in a disease context. Importantly, we found that disease-specific oligodendroglia are also present in human MS brains and that a substantial number of genes known to be susceptibility genes for MS, so far mainly associated with immune cells, are expressed in the OL lineage cells. Finally, we demonstrate that OPCs can phagocytose and that MHC-II-expressing OPCs can activate memory and effector CD4-positive T cells. Our results suggest that OLs and OPCs are not passive targets but instead active immunomodulators in MS. The disease-specific OL lineage cells, for which we identify several biomarkers, may represent novel direct targets for immunomodulatory therapeutic approaches in MS.
Databáze: MEDLINE
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