Role of the chemokine receptors CXCR3, CXCR4 and CCR7 in the intramuscular recruitment of plasmacytoid dendritic cells in dermatomyositis

Abstract

To explore the possible mechanism implicated in the recruitment of plasmacytoid dendritic cells (pDCs), we investigated the expression of the chemokine receptors CXCR3, CXCR4, and CCR7 on intramuscular and circulating pDCs from patients with dermatomyositis (DM). Using immunohistochemistry, preferential expression of CXCR3, CXCR4 and CCR7 was identified in the perivascular inflammatory infiltrates within the perimysium in DM muscle. Western-blot analysis showed marked up-regulation of expression of CXCR3, CXCR4 and CCR7 in muscle homogenate from patients with DM compared with that in non-diseased controls. Co-localization of CD303+ pDCs with these chemokine receptors was further examined by double immunofluorescence staining, which showed extensive co-localization of CD303 with CXCR3/CXCR4/CCR7 in DM biopsies. Flow cytometry was then used to investigate the proportion of pDCs among the total PBMCs and the expression of CXCR3, CXCR4 and CCR7 on circulating pDCs. The proportion of CD123+CD303+ pDCs in peripheral blood from DM patients was markedly decreased compared to that from polymyositis (PM) patients and normal controls. Significantly increased expression of CXCR3, but not CXCR4 or CCR7, was further identified on circulating pDCs in DM. Correlation analysis showed that the expression of CXCR3 correlated inversely with the frequency of pDCs in peripheral blood. Our findings indicate that the chemokine receptors, CXCR3, CXCR4 and CCR7 may be involved in the recruitment of pDCs from peripheral blood to muscle tissues in DM via different mechanisms, and in which CXCR3 may play an important role under DM conditions.

Keywords: CCR7; CXCR3; CXCR4; Chemokine receptors; Dermatomyositis; Plasmacytoid dendritic cells; Type I interferon.