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Journal of Neuroinflammation

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Open Access 01-12-2021 | Research

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

Authors: Dylan Krajewski, Debayon Paul, Shujun Ge, Evan Jellison, Joel S. Pachter

Published in: Journal of Neuroinflammation | Issue 1/2021

Abstract

Background

Tight 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.

Methods

To begin clarifying the significance of CLN-5⁺ leukocytes, flow cytometry was used to determine their appearance in the blood and CNS during EAE.

Results

Flow 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.

Conclusion

Several 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.

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Title: Appearance of claudin-5+ leukocyte subtypes in the blood and CNS during progression of EAE
Authors: Dylan Krajewski
Debayon Paul
Shujun Ge
Evan Jellison
Joel S. Pachter
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2021
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-021-02328-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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