Role of ninjurin-1 in the migration of myeloid cells to central nervous system inflammatory lesions

Igal Ifergan, Hania Kebir, Simone Terouz, Jorge I. Alvarez, Marc André Lécuyer, Steve Gendron, Lyne Bourbonnière, Ildiko R. Dunay, Alain Bouthillier, Robert Moumdjian, Adriano Fontana, Arsalan Haqqani, Armelle Klopstein, Marco Prinz, Rubèn Lõpez-Vales, Thomas Birchler, Alexandre Prat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Objective: Blood-derived myeloid antigen-presenting cells (APCs) account for a significant proportion of the leukocytes found within lesions of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). These APCs along with activated microglia are thought to be pivotal in the initiation of the central nervous system (CNS)-targeted immune response in MS and EAE. However, the exact molecules that direct the migration of myeloid cells from the periphery across the blood-brain barrier (BBB) remain largely unknown. Methods: We identified Ninjurin-1 in a proteomic screen of human BBB endothelial cells (ECs). We assessed the expression of Ninjurin-1 by BBB-ECs and immune cells, and we determined the role of Ninjurin-1 in immune cell migration to the CNS in vivo in EAE mice. Results: Ninjurin-1 was found to be weakly expressed in the healthy human and mouse CNS but upregulated on BBB-ECs and on infiltrating APCs during the course of EAE and in active MS lesions. In human peripheral blood, Ninjurin-1 was predominantly expressed by monocytes, whereas it was barely detectable on T and B lymphocytes. Moreover, Ninjurin-1 neutralization specifically abrogated the adhesion and migration of human monocytes across BBB-ECs, without affecting lymphocyte recruitment. Finally, Ninjurin-1 blockade reduced clinical disease activity and histopathological indices of EAE and decreased infiltration of macrophages, dendritic cells, and APCs into the CNS. Interpretation: Our study uncovers an important cell-specific role for Ninjurin-1 in the transmigration of inflammatory APCs across the BBB and further emphasizes the importance of myeloid cell recruitment during the development of neuroinflammatory lesions.ANN NEUROL 2011

Original languageEnglish (US)
Pages (from-to)751-763
Number of pages13
JournalAnnals of neurology
Issue number5
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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