Tickets to the Brain: Role of CCR2 and CX3CR1 in Myeloid Cell Entry in the CNS

Myeloid cells are mediators of central nervous system (CNS) damage and recovery in neuroinflammatory and neurodegenerative disorders. Besides endogenous myelomonocytic cell populations that reside in the brain already during development, newly migrated leukocytes are considered as important disease modulators in the adult brain. Thus, understanding of myeloid cell recruitment is pivotal for manipulating immune cell entry into the CNS and potentially reducing disease burden. Before myeloid cells engraft in the brain, they first tether to and roll on the activated brain endothelium, then they firmly adhere and eventually transmigrate into the damaged brain where they execute effector functions and differentiate into cells with microglia-like features. These steps are mainly regulated by adhesion molecules and by chemokines and their cognate receptors. Due to recent advances in our understanding of monocyte heterogeneity, the interest in chemokine receptors has significantly increased. Among others, the presence of the chemokine receptors CCR2 and CX(3)CR(1) is considered to be critical for both myeloid cell trafficking along inflamed vessels and subsequent accumulation in the brain. Therefore, these molecules present viable targets for therapeutic manipulations of myeloid cells destined for the CNS.