Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10

KIESEIER, B. C., TANI, M., MAHAD, D., OKA, N., HO, T., WOODROOFE, N., GRIFFIN, J. W., TOYKA, K. V., RANSOHOFF, R. M. and HARTUNG, H-P. (2001). Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10. Brain, 125 (4), 823-834.

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Link to published version:: 10.1093/brain/awf070

Abstract

Inflammatory cell recruitment is an important step in the pathogenesis of autoimmune demyelinating diseases of the PNS. Chemokines might play a critical role in promoting leucocyte entry into the nervous system during immune-mediated inflammation. Here, we report the expression pattern of the chemokine receptors CCR-1, CCR-2, CCR-4, CCR-5 and CXCR-3 in sural nerve biopsies obtained from patients with classical Guillain–Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy), chronic inflammatory demyelinating polyradiculoneuropathy and various non-inflammatory neuropathies. A consistent chemokine receptor expression pattern was immunohistochemically detected in inflammatory demyelinating neuropathies and quantitation of labelled mononuclear cells revealed significantly elevated cell counts compared with controls. CCR-1 and CCR-5 were primarily expressed by endoneurial macrophages, whereas CCR-2, CCR-4 and CXCR-3 could be localized to invading T lymphocytes. Quantitative analysis revealed that CXCR-3 was expressed at highest numbers by infiltrating T cells compared with the other receptors. Thus, expression and distribution of CXCR-3 suggest a specific role of this receptor in chemokine-mediated lymphocyte traffic into the inflamed PNS tissue. Therefore, we further analysed the expression of its ligands interferon--inducible protein of 10 kDa (IP-10) and monokine induced by interferon- (Mig). Significantly increased levels of IP-10 could be measured in the CSF of patients with inflammatory neuropathies, whereas no differences were observable for Mig. In situ hybridization for IP-10 mRNA mirrored the distribution of the cognate receptor within the inflamed PNS, and delineated endothelial cells as the primary cellular source of IP-10. Our results imply a pathogenic role for specific chemokine receptors and IP-10 in the genesis of inflammatory demyelinating neuropathies.

Item Type: Article
Research Institute, Centre or Group: Biomedical Research Centre
Identification Number: 10.1093/brain/awf070
Depositing User: Ann Betterton
Date Deposited: 13 Feb 2008
Last Modified: 09 Dec 2009 18:23
URI: http://shura.shu.ac.uk/id/eprint/391

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