Current status of chemokines in the adult CNS

Chemokines – chemotactic cytokines – are small secreted proteins that attract and activate immune and non-immune cells in vitro and in vivo. It has been suggested that chemokines and their receptors play a role in the central nervous system (CNS), in addition to their well established role in the immune system. We focus here on three chemokines—CXCL12 (C-X-C motif ligand 12), CCL2 (C-C motif ligand 2), and CX3CL1 (C-X-3C motif ligand 1) – and their principal receptors – CXCR4 (C-X-C motif receptor 4), CCR2 (C-C motif receptor 2) and CX3CR1 (C-X-3C motif receptor 1), respectively. We first introduce the classification of chemokines and their G-protein coupled receptors and the main signaling pathways triggered by receptor activation. We then discuss the cellular distribution of CXCL12/CXCR4, CCL2/CCR2 and CX3CL1/CX3CR1 in adult brain and the neurotransmission and neuromodulation effects controlled by these chemokines in the adult CNS. Changes in the expression of CXCL12, CCL2 and CX3CL1 and their respective receptors are also increasingly being implicated in the pathogenesis of CNS disorders, such as Alzheimer's disease, Parkinson's disease, HIV-associated encephalopathy, stroke and multiple sclerosis, and are therefore plausible targets for future pharmacological intervention. The final section thus discusses the role of these chemokines in these pathophysiological states. In conclusion, the role of these chemokines in cellular communication may make it possible: (i) to identify new pathways of neuron–neuron, glia–glia or neuron–glia communications relevant to both normal brain function and neuroinflammatory and neurodegenerative diseases; (ii) to develop new therapeutic approaches for currently untreatable brain diseases.

► A better understanding of the role of chemokines and their receptors in the CNS in addition to the immune system.
► This review focuses on recent data about three couples CXCL12/CXCR4, CCL2/CCR2, and CX3CL1/CX3CR1 in the adult CNS.
► Description of their cellular expressions, distributions, and roles in neurotransmission and neuromodulation.
► This review summarizes current evidence on the role of these chemokine systems in the pathogenesis of CNS disorders.