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

Megha Meena; Mats Van Delen; Maxime De Laere; Ann Sterkens; Coloma Costas Romero; Zwi Berneman; Nathalie Cools

doi:10.3390/membranes11090700

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

Membranes (Basel). 2021 Sep 13;11(9):700. doi: 10.3390/membranes11090700.

Authors

Megha Meena¹, Mats Van Delen¹, Maxime De Laere^{1

2}, Ann Sterkens^{1

3}, Coloma Costas Romero¹, Zwi Berneman^{1

2}, Nathalie Cools^{1

2}

Affiliations

¹ Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium.
² Center for Cell Therapy and Regenerative Medicine, Laboratory of Experimental Hematology, Antwerp University Hospital, 2650 Edegem, Belgium.
³ Department of Dermatology, Antwerp University Hospital, 2650 Edegem, Belgium.

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: actin restructuring; blood–brain barrier; central nervous system; dendritic cells; endothelial cells; immune cells; lymphocytes; transmigration.