A Brain Endothelial Cell Caveolin-1/CXCL10 Axis Promotes T Cell Transcellular Migration Across the Blood-Brain Barrier.

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2025-01-01 Epub Date: 2025-03-10 DOI:10.1080/17590914.2025.2472070
Troy N Trevino, Ali A Almousawi, Remy Martins-Goncalves, Andrea Ochoa-Raya, KaReisha F Robinson, Genesis L Abad, Leon M Tai, Suellen D Oliveira, Richard D Minshall, Sarah E Lutz
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引用次数: 0

Abstract

The mechanisms that govern whether T cells cross blood-brain barrier (BBB) endothelium by transcellular versus paracellular routes are unclear. Caveolin-1 is a membrane scaffolding and signaling protein associated with transcellular transmigration through the endothelial cytoplasm. Here, we report that the neuroinflammatory chemokine CXCL10 induced transcellular, caveolar transmigration of CXCR3+ CD4+ T cells. Specifically, data revealed that CXCL10-induced transcellular transmigration requires expression of Caveolin-1 and ICAM-1 in brain endothelial cells and of the CXCL10 receptor, CXCR3, and LFA-1 in T cells. Moreover, Caveolin-1 promoted CXCL10 aggregation into brain endothelial cytoplasmic stores, providing a mechanism for activation and recruitment of CXCR3+ T cells to migrate at cytoplasmic locations, distal to cell-cell junctions. Consistent with our in vitro data, genetic ablation of Caveolin-1 reduces infiltration of CXCR3+ CD4+ T cells into the CNS in experimental autoimmune encephalomyelitis. Our findings establish a novel mechanism by which brain endothelial cells utilize Caveolin-1 dependent CXCL10 intracellular stores to license T cells for transcellular migration across the blood-brain barrier.

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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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