Appearance of claudin-5+ leukocyte subtypes in the blood and CNS during progression of EAE

Journal of Neuroinflammation

Joel S. Pachter¹  Dylan Krajewski¹  Shujun Ge¹  Debayon Paul²  Evan Jellison³ 

[1] Blood-Brain Barrier Laboratory, UConn Health, 263 Farmington Ave., 06030, Farmington, CT, USA;Department of Immunology, UConn Health, 263 Farmington Ave., 06030, Farmington, CT, USA;Blood-Brain Barrier Laboratory, UConn Health, 263 Farmington Ave., 06030, Farmington, CT, USA;Department of Immunology, UConn Health, 263 Farmington Ave., 06030, Farmington, CT, USA;PureTech Health, 6 Tide Street, 02210, Boston, MA, USA;Department of Immunology, UConn Health, 263 Farmington Ave., 06030, Farmington, CT, USA;

关键词: Tight junctions;    Leukocytes;    Neuroinflammation;    Blood–brain barrier;   

DOI  :  10.1186/s12974-021-02328-3

来源: Springer

【 摘 要 】

BackgroundTight junctions (TJs) are membrane specializations characteristic of barrier-forming membranes, which function to seal the aqueous pathway between endothelial cells or epithelial cells and, thereby, obstruct intercellular solute and cellular movement. However, previous work from our laboratory found that claudin-5 (CLN-5), a TJ protein prominent at the blood–brain barrier (BBB), was also detected, ectopically, on leukocytes (CLN-5+) in the blood and central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory, demyelinating disease that is a model for multiple sclerosis. CLN-5 was further shown to be transferred from endothelial cells to circulating leukocytes during disease, prompting consideration this action is coupled to leukocyte transendothelial migration (TEM) into the CNS by fostering transient interactions between corresponding leukocyte and endothelial junctional proteins at the BBB.MethodsTo begin clarifying the significance of CLN-5+ leukocytes, flow cytometry was used to determine their appearance in the blood and CNS during EAE.ResultsFlow cytometric analysis revealed CLN-5+ populations among CD4 and CD8 T cells, B cells, monocytes and neutrophils, and these appeared with varying kinetics and to different extents in both blood and CNS. CLN-5 levels on circulating T cells further correlated highly with activation state. And, the percentage of CLN-5+ cells among each of the subtypes analyzed was considerably higher in CNS tissue than in blood, consistent with the interpretation that CLN-5+ leukocytes gain preferred access to the CNS.ConclusionSeveral leukocyte subtypes variably acquire CLN-5 in blood before they enter the CNS, an event that may represent a novel mechanism to guide leukocytes to sites for paracellular diapedesis across the BBB.

【 授权许可】

CC BY