Centre de Recherche du CHUM
Neurosciences

Author Of 1 Presentation

Pathogenesis – the Blood-Brain Barrier Late Breaking Abstracts

LB1270 - DICAM : A new cell adhesion molecule involved in myeloid cells infiltration in Multiple Sclerosis (ID 2168)

Speakers
Presentation Number
LB1270
Presentation Topic
Pathogenesis – the Blood-Brain Barrier

Abstract

Background

Disruption of the blood-brain barrier (BBB) and migration of leukocytes from the periphery to the central nervous system (CNS) are early events in lesion formation during multiple sclerosis (MS). Among CNS-infiltrated leukocytes, macrophages and dendritic cells are important contributors to inflammation and tissue damage. They readily cross the BBB to infiltrate the CNS and express pro-inflammatory cytokines. Using proteomic and RNA sequencing techniques, we have identified Dual Ig domain containing Cell Adhesion Molecule (DICAM) as a new adhesion molecule expressed by human TH17 lymphocytes and BBB endothelial cells (ECs). The expression and function of DICAM in MS pathogenesis remain unexplored.

Objectives

The current study aims to evaluate DICAM’s role in monocytes/macrophages and dendritic cells migration to the central nervous system.

Methods

To explore the DICAM expression profile, we performed flow cytometry and qPCR on human BBB-ECs and immune cells subsets isolated from healthy control peripheral blood. Confocal microscopy, flow cytometry and qPCR have been performed to explore DICAM expression in MS lesions and on peripheral immune cells in situ and ex vivo. To further investigate the expression of DICAM by myeloid cells in patients with MS, we performed flow cytometry analysis of peripheral blood mononuclear cells from males and females patients with relapsing remitting MS (n= 19), secondary progressive MS (n= 19) and primary progressive MS (n= 21) aged and sex-matched with controls individuals (n= 39) samples. The role of DICAM in monocytes adhesion to the BBB-ECs was assessed in vitro by blocking DICAM in a flow adhesion assay on a monolayer of human BBB-ECs. Different animal models of MS (EAE) were also used to explore DICAM function in vivo.

Results

We first demonstrated that DICAM and its ligand αvβ3 are upregulated on the BBB within inflammatory lesions in the brains of MS patients. In peripheral blood preliminary results indicates that DICAM expression by myeloid DCs and classical monocytes is associated with RRMS and SPMS forms of the disease. Moreover, blockade of DICAM restricts the adhesion of monocytes on human BBB-ECs and decreases disease severity in several EAE models.

Conclusions

This study aims to characterize the interaction mediated by DICAM between infiltrating leukocytes and the BBB. This adhesion molecule might be involved in MS pathogenesis and therefore, could become a new therapeutic target for MS treatment.

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