Alpha-chemokine receptors CXCR1-3 and their ligands in idiopathic inflammatory myopathies.

Abstract:

:The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of neuromuscular disorders subdivided into polymyositis (PM), sporadic inclusion body myositis (sIBM) and dermatomyositis (DM). Chemokines play an essential role in sustained inflammation associated with IIM. We studied the distribution of the alpha-chemokine receptors CXCR1, 2, 3 and their ligands interferon-gamma (IFN-gamma)-inducible T cell alpha chemoattractant (I-TAC), IFN-gamma-inducible protein of 10 kDa (IP-10), monokine induced by IFN-gamma (MIG) and growth-related oncogene (GRO) in IIM using immunohistochemistry, immunofluorescence and Western blotting. Abundant expression of IP-10 was observed on macrophages and T cells surrounding and invading non-necrotic muscle fibers in PM and sIBM and in T cells in perimysial infiltrates of DM. IP-10 was also localized to blood vessel endothelial cells in all inflammatory and normal muscle tissues. The distribution of other alpha-chemokines was variable: Only low levels of MIG and I-TAC were detected; GRO was localized to the endomysial infiltrates of some PM and sIBM samples, but not in DM. Muscle tissues were invariably CXCR1 negative, while a subset of inflammatory cells in all IIM were CXCR2 positive. Strong CXCR3 expression was observed on the majority of T cells in each IIM. We describe the differential repertoire of alpha-chemokines in IIM, and offer additional proof of the predominance of Th1-driven reactions in the immunopathogenesis of all three diagnostic subgroups. We suggest the Th1-mediated immunity in general, and the CXCR3/IP-10 interaction in particular, as potential targets for novel therapeutic intervention in IIM.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

De Paepe B,De Keyzer K,Martin JJ,De Bleecker JL

doi

10.1007/s00401-005-0989-5

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

576-82

issue

6

eissn

0001-6322

issn

1432-0533

journal_volume

109

pub_type

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