Abstract:

Distinct migratory pathways and trafficking of dendritic cells to the central nervous system (CNS): The immune system is a host defense mechanism protecting against invaders, such as bacteria and viruses, while maintaining tolerance to self. Nonetheless, a few sites throughout the body are believed to be immunologically inert, such as the testes, the eye and the brain. Indeed, experiments in the mid-20 th century gave rise to the concept of the brain as a site of immune privilege. Originally, the immune privilege of the brain was thought to be absolute, attributed by a physical blood-brain barrier (BBB) protecting the CNS from the entry of pathogens and circulating immune cells. These views have changed and currently, the CNS is seen as an immune-specialized site regulated by immunological components into and within the CNS. However, in neuroinflammatory disorders, such as multiple sclerosis (MS), the resident and infiltrating immune cells damage components of the CNS resulting in neurodegeneration. Among the various immune cells that infiltrate the CNS are dendritic cells (DCs), professional antigen-presenting cells capable to initiate both immunity and tolerance. DCs are known to transmigrate into the CNS during neuro-inflammation via different routes, one of them is through the activation and breakdown of the BBB. The infiltration of peripheral DCs in the CNS follow a classical multistep model, which are arbitrated by the expression of chemokine receptors and adhesion molecules on the surface of DCs). Previous findings from our group have demonstrated aberrant expression of migration markers and increased chemotaxis, besides aberrant expression of maturation markers, by circulating DCs of MS patients as compared to DCs from healthy controls. A better understanding of immune cell infiltration, explicitly DC transmigration into the CNS, can provide a better comprehension of the underlying processes driving neuroinflammation, such as in MS, ultimately moving forward the field by identifying new treatment targets. Indeed, although currently available therapeutics can modulate immune cell migration in general, selective hampering of pathogenic DC recruitment into the CNS in particular, might form the basis for the design of new therapeutic strategies for MS.