Myelin-reactive B cells exacerbate CD4 + T cell-driven CNS autoimmunity in an IL-23-dependent manner.

Autor: Fazazi MR; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada., Doss PMIA; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada., Pereira R; Krembil Research Institute, University Health Network, Toronto, M5T 0S8, ON, Canada., Fudge N; Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada.; Department of Neurology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada., Regmi A; Krembil Research Institute, University Health Network, Toronto, M5T 0S8, ON, Canada.; Department of Immunology, University of Toronto, Toronto, M5S 1A1, ON, Canada., Joly-Beauparlant C; axe Endocrinologie et nephrologie, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, QC, G1V 4G2, Canada., Akbar I; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada., Yeola AP; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada., Mailhot B; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada., Baillargeon J; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada., Grenier P; axe Endocrinologie et nephrologie, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, QC, G1V 4G2, Canada., Bertrand N; axe Endocrinologie et nephrologie, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, QC, G1V 4G2, Canada.; Faculty of Pharmacy, Laval University, 1050 ave de la Médecine, Quebec City, QC, G1V 4G2, Canada., Lacroix S; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada.; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050 ave de la Médecine, Quebec City, QC, G1V 4G2, Canada., Droit A; axe Endocrinologie et nephrologie, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, QC, G1V 4G2, Canada.; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050 ave de la Médecine, Quebec City, QC, G1V 4G2, Canada., Moore CS; Division of BioMedical Sciences, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada.; Department of Neurology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada., Rojas OL; Krembil Research Institute, University Health Network, Toronto, M5T 0S8, ON, Canada.; Department of Immunology, University of Toronto, Toronto, M5S 1A1, ON, Canada., Rangachari M; axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada. manu.rangachari@crchudequebec.ulaval.ca.; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050 ave de la Médecine, Quebec City, QC, G1V 4G2, Canada. manu.rangachari@crchudequebec.ulaval.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 26; Vol. 15 (1), pp. 5404. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1038/s41467-024-49259-0
Abstrakt: B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH [MOG] mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG [35-55] , IgH [MOG] mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH [MOG] meninges and by CD4 + T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH [MOG] CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH [MOG] mice. In the CNS parenchyma and dura mater of IgH [MOG] mice, we observe an increased frequency of CD4 + PD-1 + CXCR5 - T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH [MOG] mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner.
(© 2024. The Author(s).)
Databáze: MEDLINE
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