Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack - Archive ouverte HAL Access content directly
Journal Articles Brain Communications Year : 2022

Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack

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Abstract

Abstract Contact-mediated interactions between the astrocytic endfeet and infiltrating immune cells within the perivascular space are underexplored, yet represent potential regulatory check-points against CNS autoimmune disease and disability. Reactive astrocytes upregulate junctional adhesion molecule-A, an immunoglobulin-like cell surface receptor that binds to T cells via its ligand, the integrin, lymphocyte function-associated antigen-1. Here, we tested the role of astrocytic junctional adhesion molecule-A in regulating CNS autoinflammatory disease. In cell co-cultures, we found that junctional adhesion molecule-A-mediated signalling between astrocytes and T cells increases levels of matrix metalloproteinase-2, C–C motif chemokine ligand 2 and granulocyte-macrophage colony-stimulating factor, pro-inflammatory factors driving lymphocyte entry and pathogenicity in multiple sclerosis and experimental autoimmune encephalomyelitis, an animal model of CNS autoimmune disease. In experimental autoimmune encephalomyelitis, mice with astrocyte-specific JAM-A deletion (mGFAP:CreJAM-Afl/fl) exhibit decreased levels of matrix metalloproteinase-2, reduced ability of T cells to infiltrate the CNS parenchyma from the perivascular spaces and a milder histopathological and clinical course of disease compared with wild-type controls (JAM-Afl/fl). Treatment of wild-type mice with intraperitoneal injection of soluble junctional adhesion molecule-A blocking peptide decreases the severity of experimental autoimmune encephalomyelitis, highlighting the potential of contact-mediated astrocyte–immune cell signalling as a novel translational target against neuroinflammatory disease.
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Dates and versions

inserm-03627220 , version 1 (01-04-2022)

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Mario Amatruda, Candice Chapouly, Viola Woo, Farinaz Safavi, Joy Zhang, et al.. Astrocytic junctional adhesion molecule-A regulates T-cell entry past the glia limitans to promote central nervous system autoimmune attack. Brain Communications, 2022, 4 (2), pp.fcac044. ⟨10.1093/braincomms/fcac044⟩. ⟨inserm-03627220⟩

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