title: Cutting Edge: CD99 Is a Novel Therapeutic Target for Control of T Cell-Mediated Central Nervous System Autoimmune Disease.
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.
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and.
authors.forename: Ryan C
authors.identifier: http://orcid.org/0000-0001-9160-6646
authors.initials: RC
authors.lastname: Winger
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors.forename: Christopher T
authors.identifier: http://orcid.org/0000-0001-7000-8743
authors.initials: CT
authors.lastname: Harp
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chiang
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and.
authors.forename: David P
authors.identifier: http://orcid.org/0000-0002-7462-3898
authors.initials: DP
authors.lastname: Sullivan
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Watson
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and.
authors.forename: Evan W
authors.initials: EW
authors.lastname: Weber
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors.forename: Joseph R
authors.identifier: http://orcid.org/0000-0002-5818-8515
authors.initials: JR
authors.lastname: Podojil
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; and wamuller@northwestern.edu.
authors.forename: William A
authors.identifier: http://orcid.org/0000-0002-4802-2757
authors.initials: WA
authors.lastname: Muller
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology; D001402:B-Lymphocytes; D001812:Blood-Brain Barrier / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D051379:Mice
chemical_list: D000071443:12E7 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules