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Front Cell Neurosci. 2014 May 28;8:154. doi: 10.3389/fncel.2014.00154. eCollection 2014.

Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers.

Author information

  • 1Department of Internal Medicine, Washington University School of Medicine St. Louis, MO, USA.
  • 2Infectious Diseases Division, Decision Resources Group Burlington, MA, USA.
  • 3Department of Internal Medicine, Washington University School of Medicine St. Louis, MO, USA ; Department of Pathology and Immunology, Washington University School of Medicine St. Louis, MO, USA ; Department of Anatomy and Neurobiology, Washington University School of Medicine St. Louis, MO, USA.

Abstract

In the adult central nervous system (CNS), chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier (BBB) including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

KEYWORDS:

blood brain barrier; central nervous system; chemokines; choroid plexus; homeostasis; meninges; neurogenesis; vasculature

PMID:
24920943
[PubMed]
PMCID:
PMC4036130
Free PMC Article

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