Selective expression of claudin-5 in thymic endothelial cells regulates the blood–thymus barrier and T-cell export

How claudin-5 regulates the blood-thymus barrier Abstract T-cell development depends on the thymic microenvironment, in which endothelial cells (ECs) play a vital role. Interestingly, vascular permeability of the thymic cortex is lower than in other organs, suggesting the existence of a blood–thymus...

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Published in:International immunology 2021-03, Vol.33 (3), p.171-182
Main Authors: Nagatake, Takahiro, Zhao, Yan-Chun, Ito, Takeshi, Itoh, Masahiko, Kometani, Kohei, Furuse, Mikio, Saika, Azusa, Node, Eri, Kunisawa, Jun, Minato, Nagahiro, Hamazaki, Yoko
Format: Article
Language:English
Subjects:
Animals
Capillary Permeability - physiology
Cell Differentiation - immunology
Cell Line
Claudin-5 - biosynthesis
Claudin-5 - metabolism
Editor's Choice
Endothelial Cells - metabolism
Lysophospholipids - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Sphingosine - analogs & derivatives
Sphingosine - metabolism
T-Lymphocytes - cytology
T-Lymphocytes - metabolism
Thymocytes - metabolism
Thymus Gland - metabolism
Tight Junctions - physiology
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Summary:How claudin-5 regulates the blood-thymus barrier Abstract T-cell development depends on the thymic microenvironment, in which endothelial cells (ECs) play a vital role. Interestingly, vascular permeability of the thymic cortex is lower than in other organs, suggesting the existence of a blood–thymus barrier (BTB). On the other hand, blood-borne molecules and dendritic cells bearing self-antigens are accessible to the medulla, facilitating central tolerance induction, and continuous T-precursor immigration and mature thymocyte egress occur through the vessels at the cortico-medullary junction (CMJ). We found that claudin-5 (Cld5), a membrane protein of tight junctions, was expressed in essentially all ECs of the cortical vasculatures, whereas approximately half of the ECs of the medulla and CMJ lacked Cld5 expression. An intravenously (i.v.) injected biotin tracer hardly penetrated cortical Cld5+ vessels, but it leaked into the medullary parenchyma through Cld5– vessels. Cld5 expression in an EC cell line caused a remarkable increase in trans-endothelial resistance in vitro, and the biotin tracer leaked from the cortical vasculatures in Cldn5–/– mice. Furthermore, i.v.-injected sphingosine-1 phosphate distributed selectively into the medulla through the Cld5– vessels, probably ensuring the egress of CD3high mature thymocytes from Cld5– vessels at the CMJ. These results suggest that distinct Cld5 expression profiles in the cortex and medulla may control the BTB and the T-cell gateway to blood circulation, respectively.
ISSN:1460-2377
0953-8178
1460-2377
DOI:10.1093/intimm/dxaa069