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

Mohamed Reda Fazazi, Prenitha Mercy Ignatius Arokia Doss, Resel Pereira, Neva Fudge, Aryan Regmi, Charles Joly-Beauparlant, Irshad Akbar, Asmita Pradeep Yeola, Benoit Mailhot, Joanie Baillargeon, Philippe Grenier, Nicolas Bertrand, Steve Lacroix, Arnaud Droit, Craig S. Moore, Olga L. Rojas and Manu Rangachari ()
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Mohamed Reda Fazazi: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Prenitha Mercy Ignatius Arokia Doss: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Resel Pereira: University Health Network
Neva Fudge: Memorial University of Newfoundland
Aryan Regmi: University Health Network
Charles Joly-Beauparlant: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Irshad Akbar: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Asmita Pradeep Yeola: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Benoit Mailhot: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Joanie Baillargeon: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Philippe Grenier: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Nicolas Bertrand: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Steve Lacroix: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Arnaud Droit: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL
Craig S. Moore: Memorial University of Newfoundland
Olga L. Rojas: University Health Network
Manu Rangachari: Centre de recherche du Centre hospitalier universitaire (CHU) de Québec – Université Laval, Pavillon CHUL

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-49259-0

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