Transmigration across a Steady-State Blood–Brain Barrier Induces Activation of Circulating Dendritic Cells Partly Mediated by Actin Cytoskeletal Reorganization

Abstract

The central nervous system (CNS) is considered to be an immunologically unique site, in large part given its extensive protection by the blood–brain barrier (BBB). As our knowledge of the complex interaction between the peripheral immune system and the CNS expands, the mechanisms of immune privilege are being refined. Here, we studied the interaction of dendritic cells (DCs) with the BBB in steady–state conditions and observed that transmigrated DCs display an activated phenotype and stronger T cell-stimulatory capacity as compared to non-migrating DCs. Next, we aimed to gain further insights in the processes underlying activation of DCs following transmigration across the BBB. We investigated the interaction of DCs with endothelial cells as well as the involvement of actin cytoskeletal reorganization. Whereas we were not able to demonstrate that DCs engulf membrane fragments from fluorescently labelled endothelial cells during transmigration across the BBB, we found that blocking actin restructuring of DCs by latrunculin-A significantly impaired in vitro migration of DC across the BBB and subsequent T cell-stimulatory capacity, albeit no effect on migration-induced phenotypic activation could be demonstrated. These observations contribute to the current understanding of the interaction between DCs and the BBB, ultimately leading to the design of targeted therapies capable to inhibit autoimmune inflammation of the CNS.

Keywords

• central nervous system
• dendritic cells
• blood–brain barrier
• immune cells
• endothelial cells
• lymphocytes