Myeloid Dendritic Cells Are Major Producers of IFN-β in Dermatomyositis and May Contribute to Hydroxychloroquine Refractoriness

Dermatomyositis pathogenesis remains incompletely understood; however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-beta, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-beta in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-beta by immunofluorescence and laser-capture microdissection revealed increased IFN-beta mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-beta in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-beta in healthy controls (P < 0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P < 0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-beta production.

Automated summary

The pathogenesis of dermatomyositis involves a predominant IFN-1 response, with mDCs playing an important role in IFN-beta production in the skin. Patients with dermatomyositis have increased CD4+, CD11c+, and CD69+ cells in lesional skin, and both mDCs and plasmacytoid dendritic cells are major producers of IFN-beta in their blood. Additionally, mDCs are significantly increased in the skin of hydroxychloroquine nonresponders.