Chemokines and their receptors: The importance of their expression for an appropriate regulation of the immune response in health and disease.

Abstract

Leukocytes are typically migratory immune cells, and their migration is of critical immunological importance. In this context, chemokines and their receptors play a dynamic role in regulating the functions of leukocytes within the immune system, since they drive leukocytes into and out of blood and lymphatic vessels and direct their interstitial movement and positioning. Chemokines constitute a large family of cytokines that primarily regulate immune cell migration through the binding to chemokine receptors expressed on the surface of leukocytes. They are expressed by both immune and non-immune cells, and their activity is tightly regulated at several levels from transcription to secretion and distribution. Conventional chemokine receptors are G protein-coupled receptors (GPCR) found mainly in immune cells that can modulate the immune response activation by the initiation of a signaling cascade. On the contrary, atypical chemokine receptors act as decoy receptors and regulate chemokine levels in the blood. Together, chemokines and their receptors form the chemokine system, a complex network with high redundance and promiscuity. Dysregulation of this system can contribute to various disorders that have an immune or inflammatory component mediated by chemokine-directed leukocyte migration, such as chronic inflammatory and neurodegenerative disorders. Thus, in this chapter I focused on the role of chemokines and their receptors under physiological conditions and on their implication in disorders like multiple sclerosis, Parkinson's Disease and Alzheimer's Disease, in which neuroinflammation caused by the infiltration of these immune cells into the CNS and their activation plays a key role in the development of the pathologies.