Review
Chemokines in the brain: neuroimmunology and beyond

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Abstract

Chemokines in the brain have been recognised as essential elements in neurodegenerative diseases and related neuroinflammation. Recent studies suggest that in addition to the orchestration of chemotaxis of immune cells, chemokines are also involved in neurodevelopment and neurophysiological signalling.

Introduction

Because of extensive research and rapid progress in the field, a variety of reviews on chemokines have appeared recently that address their function and localisation, including discussion of the central nervous system (CNS) 1., 2., 3., 4., 5.. Research on chemokines in the brain has primarily focused on immune responses and local inflammation. Recently, new functions of chemokines have been described, such as their involvement in neuronal development, nociception and synaptic transmission. This review discusses recent advances in understanding the physiological and pathophysiological functions and the localisation of chemokines and their receptors in the brain.

Section snippets

Chemokines and chemokine receptors: pharmacology and function

Chemokines constitute a superfamily of small proteins (8–14 kDa) that are instrumental for the trafficking of leukocytes in normal immunosurveillance as well as the coordination of infiltration of inflammatory cells under pathological conditions. Chemokines and their receptors form an elaborate signalling system. Currently, approximately 50 different human chemokines have been described and these chemokines interact with 18 different chemokine receptors 6•., 7•..

Chemokines are classified by

Chemokines and chemokine receptors in the CNS

The first findings showing prominent expression of chemokines and their receptors in brain tissue were published approximately 10 years ago (see for example: 12., 13.). Since then, numerous detailed studies on CNS chemokines and chemokine receptors have been published, and it is now clear that the endogenous cells of the CNS synthesise distinct chemokines and might respond to chemokinestimulation by chemokine receptor expression 1., 2., 3., 4., 5..

Several lines of evidence indicate that all

Neuroinflammation

In the brain, chemokines mediate local immune responses and also attract leukocytes, which are believed to migrate along a concentration gradient of chemokines across the blood–brain barrier to their target (Fig. 1). Astrocytes and microglia are CNS-resident immune cells that can produce different kinds of chemokines. Because these glia cells are closely associated with the blood–brain barrier, it has been suggested that these cells regulate leukocyte infiltration into the brain [37•]. In

Conclusions

It is now believed that complex combinations of chemokines are involved in the specific recruitment of immune cells in the brain. Although the involvement of a large number of chemokines with overlapping biological activity suggests redundancy of this signalling system, the specific knockout of chemokine genes has been shown to prevent pathological processes in disease models in experimental animals. In addition, novel functions concerning intercellular signalling may be involved in maintaining

References and recommended reading

Papers of particular interest, published within the annual period of review,have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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