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Role of ninjurin‐1 in the migration of myeloid cells to central nervous system inflammatory lesions
Author(s) -
Ifergan Igal,
Kebir Hania,
Terouz Simone,
Alvarez Jorge I.,
Lécuyer MarcAndré,
Gendron Steve,
Bourbonnière Lyne,
Dunay Ildiko R.,
Bouthillier Alain,
Moumdjian Robert,
Fontana Adriano,
Haqqani Arsalan,
Klopstein Armelle,
Prinz Marco,
LópezVales Rubèn,
Birchler Thomas,
Prat Alexandre
Publication year - 2011
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22519
Subject(s) - microglia , immunology , immune system , myeloid , central nervous system , experimental autoimmune encephalomyelitis , encephalomyelitis , multiple sclerosis , inflammation , biology , blood–brain barrier , neuroscience
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