CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis
Antoine Fournier, Stéphanie Zandee, Marc Charabati, Evelyn Peelen, Olivier Tastet, Jorge I. Alvarez, Hania Kébir, Lyne Bourbonnière, Sandra Larouche, Boaz Lahav, Wendy Klément, Fiona Tea, Alain Bouthillier, Robert Moumdjian, Romain Cayrol, Pierre Duquette, Marc Girard, Catherine Larochelle, Nathalie Arbour, Alexandre Prat
Abstract
BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), peripheral immune cells use various cell trafficking molecules to infiltrate the CNS where they cause damage.The objective of this study was to investigate the involvement of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the CNS of patients with MS. METHODS: Expression of CLMP was measured in primary cultures of human brain endothelial cells (HBECs) and human meningeal endothelial cells (HMECs), postmortem brain samples, and peripheral blood mononuclear cells (PBMCs) from patients with MS and controls by RNA sequencing, quantitative PCR, immunohistochemistry, and flow cytometry. In vitro migration assays using HBECs and HMECs were performed to evaluate the function of CLMP. RESULTS: immune cell infiltrates in the perivascular area of parenchymal lesions and in the meninges of patients with MS. DISCUSSION: Collectively, our data demonstrate that CLMP is an adhesion molecule used by immune cells to access the CNS during neuroinflammatory disorders such as MS. CLMP could represent a target for a new treatment of neuroinflammatory conditions.