Endothelial Cell-Derived Soluble CD200 Determines the Ability of Immune Cells to Cross the Blood-Brain Barrier

The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2024-09, Vol.25 (17), p.9262
Main Authors: Pujol, Myriam, Paskevicius, Tautvydas, Robinson, Alison, Dhillon, Simran, Eggleton, Paul, Ferecskó, Alex S, Gutowski, Nick, Holley, Janet, Smallwood, Miranda, Newcombe, Jia, Agellon, Luis B, Michalak, Marek
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens, CD - genetics
Antigens, CD - metabolism
Blood vessels
Blood-Brain Barrier - immunology
Blood-Brain Barrier - metabolism
Brain - immunology
Brain - metabolism
Cell Adhesion
Cell adhesion & migration
Cytokines
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - metabolism
Encephalomyelitis, Autoimmune, Experimental - pathology
Endothelial Cells - immunology
Endothelial Cells - metabolism
Flow cytometry
Gene expression
Humans
Leukocytes
Mice
Mice, Inbred C57BL
Proteins
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion. In a tissue culture model of the blood-brain barrier, antagonizing the interaction of CD200 and sCD200 with T-cell CD200 receptor (CD200R1) via anti-CD200 blocking antibodies or the RNAi-mediated inhibition of CD200 production by endothelial cells increased T-cell adhesion and transmigration across monolayers of endothelial cells. Our findings demonstrate that sCD200 produced by brain endothelial cells regulates immune cell trafficking through the blood-brain barrier and is primarily responsible for preventing activated T-cells from entering the brain.
ISSN:1661-6596
1422-0067
1422-0067
DOI:10.3390/ijms25179262