Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis
Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis
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DOI：
10.1002/art.22558
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发表时间：
2007-05-01
影响因子：
--
通讯作者：
Reed, Ann M.
中科院分区：
文献类型：
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作者：
de Padilla, Consuelo M. Lopez;Vallejo, Abbe N.;Reed, Ann M.
Objective.目的探讨树突状细胞（DC）是否是幼年型皮肌炎（DM）肌肉炎症的组成部分。应用免疫荧光法检测幼年型DM患者炎症肌肉组织和对照组非炎症肌肉组织中DC亚群的类型、数量和活化状态。用激光捕获显微切割和定量聚合酶链反应检测肌浸润细胞趋化因子的表达。浆细胞样DC是幼年DNI患者发炎肌肉组织的主要成分。这些细胞通过共表达CD4和CD123而不是CD11c来鉴定，并且还表达CD83，表明细胞成熟。相反，在非炎症肌肉中，浆细胞样DC很少，不表达CD83。发炎肌肉血管周围的单核细胞含有丰富的CCL19和CCL21转录本，但CCL18转录本很少。相比之下，来自非炎症肌肉的细胞含有可忽略不计的CCL19和CCL21，但具有大量的CCL18。炎症和非炎症肌肉组织中CXCL 12转录本水平相当，但炎症肌肉中CXCL 12受体CXCR 4转录本水平较高。这些发现与浆细胞样DC是青少年DM肌肉炎症介质的观点一致。CD83+浆细胞样DC在血管周围区域的丰度和CCL19和CCL21在血管周围细胞灶中的过表达表明，驻留浆细胞样DC的原位激活和成熟是幼年DM肌肉炎症的起始和持续的核心。
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.