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

Area of Science:

• Immunology
• Neuroscience
• Cell Biology

Background:

• T cell transmigration across the blood-brain barrier (BBB) is crucial for central nervous system (CNS) immunity and disease.
• The specific mechanisms dictating transcellular versus paracellular routes of T cell migration remain incompletely understood.
• Caveolin-1 is implicated in transcellular transport through endothelial cells.

Purpose of the Study:

• To elucidate the mechanisms governing T cell transmigration routes across the BBB.
• To investigate the role of Caveolin-1 in T cell migration induced by the chemokine CXCL10.
• To identify the molecular players involved in CXCL10-mediated transcellular T cell migration.

Main Methods:

• Utilized in vitro models of brain endothelial cells and primary T cells.
• Investigated the expression of key proteins including Caveolin-1, ICAM-1, CXCR3, and LFA-1.
• Employed genetic ablation of Caveolin-1 in a mouse model of experimental autoimmune encephalomyelitis (EAE).

Main Results:

• CXCL10 induced transcellular, caveolar transmigration of CXCR3+ CD4+ T cells.
• This process required Caveolin-1 and ICAM-1 in endothelial cells, and CXCR3 and LFA-1 in T cells.
• Caveolin-1 facilitated intracellular CXCL10 aggregation, promoting T cell migration at distal cytoplasmic sites.

Conclusions:

• Established a novel mechanism where brain endothelial cells use Caveolin-1-dependent CXCL10 stores to facilitate T cell transcellular migration across the BBB.
• Demonstrated that Caveolin-1 is essential for CXCL10-induced T cell transmigration.
• Showed that genetic deletion of Caveolin-1 reduces T cell infiltration into the CNS in an EAE model.