Chemokines: The nexus between immunobiology and neurobiology
Inflammation of the central nervous system (CNS) entails varied levels of activation of resident microglia, macroglia and vascular elements, occasionally culminating in recruitment of hematogenous leukocytes. Thus defined, inflammation accompanies most neurological disorders, including multiple sclerosis (MS), stroke, neoplasia, trauma and HIV-1-associated dementia, as well as Alzheimer’s disease and other primary neurodegenerations. Chemokines comprise a family of peptides that act through G protein-coupled receptors (GPCRs) to regulate leukocyte migration throughout all tissues, in an exquisitely specific and flexible fashion. Initial studies asked how chemokines and chemokine receptors governed inflammatory cell recruitment to the CNS during immune-mediated or virus-induced inflammation. Later, it became clear that constitutive and inducible CNS chemokines signal to resident CNS cells, to support developmental and neurophysiological functions as well as regulating the activation of microglia, and the inflammatory functions of astrocytes. Because GPCRs are drug targets, these results have implications for the understanding and treatment of disease.