Targeting molecules involved in immune cell trafficking to the central nervous system for therapy in multiple sclerosis

Abstract

The entry of immune cells into the central nervous system (CNS) for immune surveillance occurs during normal physiological conditions, although it is difficult to detect. However, during CNS autoimmune diseases, such as multiple sclerosis and its animal model experimental autoimmune encephalomyelitis, immune cells extensively invade the CNS. Understanding the mechanisms of immune cell migration and entry into the CNS provides a plan for the development of novel therapeutics. A goal would be to target specific molecules and/or pathways, and thereby modulate inflammatory cell migration into the CNS, which ideally could suppress disease progression without compromising beneficial immune surveillance. In the present review, we highlight the key mechanisms that directly or indirectly traffic and pass immune cells, particularly T cells to the CNS. We illuminate and focus on the following matters: T-cell licensing, regional neural stimulations, gut–CNS communications and integrin-mediated cell adhesion. We discuss currently approved drugs that target T-cell migration to the CNS.