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

Autor: Pujol M; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada., Paskevicius T; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada., Robinson A; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada., Dhillon S; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada., Eggleton P; Revolo Biotherapeutics, Gaithersburg, MD 20878, USA.; University of Exeter Medical School, University of Exeter, Exeter EX1 2HZ, UK., Ferecskó AS; University of Exeter Medical School, University of Exeter, Exeter EX1 2HZ, UK., Gutowski N; University of Exeter Medical School, University of Exeter, Exeter EX1 2HZ, UK., Holley J; University of Exeter Medical School, University of Exeter, Exeter EX1 2HZ, UK., Smallwood M; University of Exeter Medical School, University of Exeter, Exeter EX1 2HZ, UK., Newcombe J; NeuroResource, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1E 6BT, UK., Agellon LB; School of Human Nutrition, McGill University, Sainte Anne de Bellevue, QC H9X 3V9, Canada., Michalak M; Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Aug 27; Vol. 25 (17). Date of Electronic Publication: 2024 Aug 27.
DOI: 10.3390/ijms25179262
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje