title: Melanoma cell adhesion molecule identifies encephalitogenic T lymphocytes and promotes their recruitment to the central nervous system.
abstract: In multiple sclerosis, encephalitogenic CD4(+) lymphocytes require adhesion molecules to accumulate into central nervous system inflammatory lesions. Using proteomic techniques, we identified expression of melanoma cell adhesion molecule (MCAM) on a subset of human effector memory CD4(+) lymphocytes and on human blood-brain barrier endothelium. Herein, we demonstrate that MCAM is a stable surface marker that refines the identification of interleukin 17(+), interleukin 22(+), RAR-related orphan receptor γ and interleukin 23 receptor(+) cells within the CD161(+)CCR6(+) subset of memory CD4(+) lymphocytes. We also show that MCAM(+) lymphocytes express significantly more granulocyte/macrophage colony stimulating factor and granzyme B than MCAM(-) lymphocytes. Furthermore, the proportion of MCAM(+) CD4(+) lymphocytes is significantly increased in the blood and in the central nervous system of patients with multiple sclerosis and experimental autoimmune encephalomyelitis animals compared with healthy controls or other neurological diseases, and MCAM expression is upregulated at the blood-brain barrier within inflammatory lesions. Moreover, blockade of MCAM or depletion of MCAM(+) CD4(+) T lymphocytes both restrict the migration of T(H)17 lymphocytes across blood-brain barrier endothelial cells and decrease the severity of experimental autoimmune encephalomyelitis. Our findings indicate that MCAM could serve as a potential biomarker for multiple sclerosis and represents a valuable target for the treatment of neuroinflammatory conditions.
authors.affiliation: Neuroimmunology Research Laboratory, Centre of Excellence in Neuromics, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, H2L 2W5, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Larochelle
authors.forename: Romain
authors.initials: R
authors.lastname: Cayrol
authors.forename: Hania
authors.initials: H
authors.lastname: Kebir
authors.forename: Jorge Ivan
authors.initials: JI
authors.lastname: Alvarez
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Lécuyer
authors.forename: Igal
authors.initials: I
authors.lastname: Ifergan
authors.forename: Émilie
authors.initials: É
authors.lastname: Viel
authors.forename: Lyne
authors.initials: L
authors.lastname: Bourbonnière
authors.forename: Diane
authors.initials: D
authors.lastname: Beauseigle
authors.forename: Simone
authors.initials: S
authors.lastname: Terouz
authors.forename: Lamia
authors.initials: L
authors.lastname: Hachehouche
authors.forename: Steve
authors.initials: S
authors.lastname: Gendron
authors.forename: Josée
authors.initials: J
authors.lastname: Poirier
authors.forename: Céline
authors.initials: C
authors.lastname: Jobin
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Ken
authors.initials: K
authors.lastname: Flanagan
authors.forename: Ted
authors.initials: T
authors.lastname: Yednock
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arbour
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051929:CD146 Antigen / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020078:Neurogenic Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D051929:CD146 Antigen; C497902:MCAM protein, human