Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system

Romain Cayrol, Karolina Wosik, Jennifer L. Berard, Aurore Dodelet-Devillers, Igal Ifergan, Hania Kebir, Arsalan S. Haqqani, Katharina Kreymborg, Sebastian Krug, Robert Moumdjian, Alain Bouthillier, Burkhard Becher, Nathalie Arbour, Samuel David, Danica Stanimirovic, Alexandre Prat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

348 Scopus citations

Abstract

Adhesion molecules of the immunoglobulin superfamily are crucial effectors of leukocyte trafficking into the central nervous system. Using a lipid raft-based proteomic approach, we identified ALCAM as an adhesion molecule involved in leukocyte migration across the blood-brain barrier (BBB). ALCAM expressed on BBB endothelium localized together with CD6 on leukocytes and with BBB endothelium transmigratory cups. ALCAM expression on BBB cells was upregulated in active multiple sclerosis and experimental autoimmune encephalomyelitis lesions. Moreover, ALCAM blockade restricted the transmigration of CD4+ lymphocytes and monocytes across BBB endothelium in vitro and in vivo and reduced the severity and delayed the time of onset of experimental autoimmune encephalomyelitis. Our findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain and identify ALCAM as a potential target for the therapeutic dampening of neuroinflammation.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalNature Immunology
Volume9
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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