Cutting Edge: CD99 Is a Novel Therapeutic Target for Control of T Cell-Mediated Central Nervous System Autoimmune Disease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ryan C WingerWilliam A Muller

Abstract

Leukocyte trafficking into the CNS is a prominent feature driving the immunopathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Blocking the recruitment of inflammatory leukocytes into the CNS represents an exploitable therapeutic target; however, the adhesion molecules that specifically regulate the step of leukocyte diapedesis into the CNS remain poorly understood. We report that CD99 is critical for lymphocyte transmigration without affecting adhesion in a human blood-brain barrier model. CD99 blockade in vivo ameliorated experimental autoimmune encephalomyelitis and decreased the accumulation of CNS inflammatory infiltrates, including dendritic cells, B cells, and CD4(+) and CD8(+) T cells. Anti-CD99 therapy was effective when administered after the onset of disease symptoms and blocked relapse when administered therapeutically after disease symptoms had recurred. These findings underscore an important role for CD99 in the pathogenesis of CNS autoimmunity and suggest that it may serve as a novel therapeutic target for controlling neuroinflammation.

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Citations

Nov 22, 2016·Scandinavian Journal of Gastroenterology·Guangxi ZhouZhanju Liu
Jan 7, 2018·Journal of Cell Communication and Signaling·Michela PaselloKatia Scotlandi
May 24, 2018·Journal of Leukocyte Biology·Maryna SamusDietmar Vestweber
Feb 8, 2018·Acta Neuropathologica·Stefan LiebnerGabriela Constantin
Dec 23, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tillmann BedauChristoph Becker-Pauly
Jul 12, 2017·Proceedings of the National Academy of Sciences of the United States of America·Wei JiangJunwei Hao
Nov 2, 2019·International Journal of Molecular Sciences·Mariana Castro DiasBritta Engelhardt
Dec 18, 2020·Frontiers in Immunology·Justin KillickAnne L Astier
Dec 11, 2020·Molecular Medicine·Mohammad Javad MousaviSomayeh Ghotloo
Nov 20, 2020·Fluids and Barriers of the CNS·Hossam KadryLuca Cucullo

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