دورية أكاديمية
أعرض في EDS

ALCAM on human oligodendrocytes mediates CD4 T cell adhesion.

التفاصيل البيبلوغرافية
العنوان: ALCAM on human oligodendrocytes mediates CD4 T cell adhesion.
المؤلفون: Jamann H; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Desu HL; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada., Cui QL; Neuroimmunology Unit, Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Canada., Halaweh A; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Microbiology, Immunology and Infectiology, Université de Montréal, Montreal, H2X 3E4, Canada., Tastet O; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada., Klement W; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada., Zandee S; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Pernin F; Neuroimmunology Unit, Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Canada., Mamane VH; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Ouédraogo O; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Microbiology, Immunology and Infectiology, Université de Montréal, Montreal, H2X 3E4, Canada., Daigneault A; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada., Sidibé H; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Millette F; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Peelen E; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Dhaeze T; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Hoornaert C; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Rébillard RM; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Thai K; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Grasmuck C; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Vande Velde C; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Prat A; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Arbour N; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada., Stratton JA; Neuroimmunology Unit, Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Canada., Antel J; Neuroimmunology Unit, Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Canada., Larochelle C; Neuroimmunology unit, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, H2X 0A9, Canada.; Department of Neurosciences, Université de Montréal, Montreal, H3T 1J4, Canada.
المصدر: Brain : a journal of neurology [Brain] 2024 Jan 04; Vol. 147 (1), pp. 147-162.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0372537 Publication Model: Print Cited Medium: Internet ISSN: 1460-2156 (Electronic) Linking ISSN: 00068950 NLM ISO Abbreviation: Brain Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Oxford University Press
Original Publication: London.
مواضيع طبية MeSH: Multiple Sclerosis* , Encephalomyelitis, Autoimmune, Experimental*, Humans ; Mice ; Animals ; CD4-Positive T-Lymphocytes/metabolism ; Activated-Leukocyte Cell Adhesion Molecule/metabolism ; Cell Adhesion ; Oligodendroglia/metabolism
مستخلص: Multiple sclerosis is a chronic neuroinflammatory disorder characterized by demyelination, oligodendrocyte damage/loss and neuroaxonal injury in the context of immune cell infiltration in the CNS. No neuroprotective therapy is available to promote the survival of oligodendrocytes and protect their myelin processes in immune-mediated demyelinating diseases. Pro-inflammatory CD4 Th17 cells can interact with oligodendrocytes in multiple sclerosis and its animal model, causing injury to myelinating processes and cell death through direct contact. However, the molecular mechanisms underlying the close contact and subsequent detrimental interaction of Th17 cells with oligodendrocytes remain unclear. In this study we used single cell RNA sequencing, flow cytometry and immunofluorescence studies on CNS tissue from multiple sclerosis subjects, its animal model and controls to characterize the expression of cell adhesion molecules by mature oligodendrocytes. We found that a significant proportion of human and murine mature oligodendrocytes express melanoma cell adhesion molecule (MCAM) and activated leukocyte cell adhesion molecule (ALCAM) in multiple sclerosis, in experimental autoimmune encephalomyelitis and in controls, although their regulation differs between human and mouse. We observed that exposure to pro-inflammatory cytokines or to human activated T cells are associated with a marked downregulation of the expression of MCAM but not of ALCAM at the surface of human primary oligodendrocytes. Furthermore, we used in vitro live imaging, immunofluorescence and flow cytometry to determine the contribution of these molecules to Th17-polarized cell adhesion and cytotoxicity towards human oligodendrocytes. Silencing and blocking ALCAM but not MCAM limited prolonged interactions between human primary oligodendrocytes and Th17-polarized cells, resulting in decreased adhesion of Th17-polarized cells to oligodendrocytes and conferring significant protection of oligodendrocytic processes. In conclusion, we showed that human oligodendrocytes express MCAM and ALCAM, which are differently modulated by inflammation and T cell contact. We found that ALCAM is a ligand for Th17-polarized cells, contributing to their capacity to adhere and induce damage to human oligodendrocytes, and therefore could represent a relevant target for neuroprotection in multiple sclerosis.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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معلومات مُعتمدة: Canada CIHR
فهرسة مساهمة: Keywords: ALCAM; MCAM; Th17 cells; multiple sclerosis; oligodendrocytes
المشرفين على المادة: 0 (Activated-Leukocyte Cell Adhesion Molecule)
0 (ALCAM protein, human)
تواريخ الأحداث: Date Created: 20230828 Date Completed: 20240108 Latest Revision: 20240829
رمز التحديث: 20240830
مُعرف محوري في PubMed: PMC10766241
DOI: 10.1093/brain/awad286
PMID: 37640028
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2156
DOI:10.1093/brain/awad286