Endothelial cells and lymphatics at the interface between the immune and central nervous systems: implications for multiple sclerosis.

Abstract

The central nervous system (CNS) has a unique relationship with the immune system. This review highlights the distinct roles of lymphatic vessels and endothelial cells in the interface between CNS and immune cells and invites to revisit the concept of CNS immune privilege. T cells can follow several routes to penetrate the CNS parenchyma but may also benefit, together with antigen-loaded presenting cells, from the newly described lymphatic network to exit the CNS. CNS endothelial cells (EC) critically positioned at the interface between circulating immune cells and the CNS regulate the multistep cascade for immune cell trafficking into the CNS. They can also be considered as semiprofessional antigen-presenting cells through their ability to present antigens to T cells and to regulate their activation through co-stimulatory and inhibitory molecules. The lymphatic network linking the CNS to draining lymph nodes may contribute to the inflammatory reaction occurring in multiple sclerosis (MS). The abundance and strategic positioning of endothelial cells at the blood-brain barrier level most likely endow them with an important role in controlling local adaptive immune responses, rendering them potential therapeutic targets in neuro-inflammatory such as MS.