Melanoma cell adhesion molecule identifies encephalitogenic T lymphocytes and promotes their recruitment to the central nervous system

Catherine Larochelle, Romain Cayrol, Hania Kebir, Jorge Ivan Alvarez, Marc André Lécuyer, Igal Ifergan, Émilie Viel, Lyne Bourbonnière, Diane Beauseigle, Simone Terouz, Lamia Hachehouche, Steve Gendron, Josée Poirier, Céline Jobin, Pierre Duquette, Ken Flanagan, Ted Yednock, Nathalie Arbour, Alexandre Prat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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 TH17 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.

Original languageEnglish (US)
Pages (from-to)2906-2924
Number of pages19
JournalBrain
Volume135
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • EAE
  • IL23
  • MCAM (CD146)
  • adhesion
  • blood-brain barrier
  • diapedesis
  • leukocyte transmigration
  • multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology

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