Journal
ARTHRITIS AND RHEUMATISM
Volume 56, Issue 5, Pages 1658-1668Publisher
WILEY-LISS
DOI: 10.1002/art.22558
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Objective. To examine whether dendritic cells (DCs) are constituents of muscle inflammation in juvenile dermatomyositis (DM). Methods. The types, numbers, and activation state of DC subsets in inflamed muscle tissue from patients with juvenile DM and in noninflamed muscle tissue from control subjects were examined by multicolor immunofluorescence. Chemokine expression of the muscle-infiltrating cells was examined by laser capture microdissection and quantitative polymerase chain reaction. Results. Plasmacytoid DCs were the predominant component of the inflamed muscle tissue from patients with juvenile DNI. These cells were identified by coexpression of CD4 and CD123, but not CD11c, and also expressed CD83, indicating maturity of the cells. In contrast, in noninflamed muscle, plasmacytoid DCs were scarce and did not express CD83. Mononuclear cells surrounding the blood vessels of inflamed muscle contained abundant transcripts of CCL19 and CCL21, but very little CCL18 transcripts. In contrast, cells from noninflamed muscle contained negligible amounts of CCL19 and CCL21, but had high amounts of CCL18. Both the inflamed and noninflamed muscle tissue had equivalent levels of CXCL12 transcripts, but inflamed muscle contained more transcripts of the CXCL12 receptor CXCR4. Conclusion. These findings are consistent with the idea that plasmacytoid DCs are mediators of muscle inflammation in juvenile DM. The abundance of CD83+ plasmacytoid DCs in perivascular areas and the overexpression of CCL19 and CCL21 in perivascular cellular foci suggest that in situ activation and maturation of resident plasmacytoid DCs are central to the initiation and perpetuation of muscle inflammation in juvenile DM.
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