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 type 1 IFN response. We explored dermatomyositis pathogenesis by quantifying inflammatory cells in skin, comparing myeloid versus plasmacytoid dendritic cell release of IFN-β, and assessing myeloid dendritic cell contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell type expression in lesional skin biopsies from 12 patients with moderate-severe cutaneous dermatomyositis. Immunofluorescence, laser capture microdissection, and flow cytometry were used to assess myeloid dendritic cell release of IFN-β in dermatomyositis lesional skin biopsies and blood. Immunohistochemistry was utilized to determine if myeloid and/or plasmacytoid dendritic cells were increased in HCQ-nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional DM skin. Myeloid dendritic cells colocalized with IFN-β via immunofluorescence and laser capture microdissection revealed increased IFN-β mRNA expression by myeloid dendritic cells in lesional DM skin. In blood, both myeloid and plasmacytoid dendritic cells were major producers of IFN-β in DM patients whereas plasmacytoid dendritic cells predominately released IFN-β in healthy controls (p < 0.01). Myeloid dendritic cells were significantly increased in skin of HCQ-nonresponders compared to responders (p < 0.05). Myeloid dendritic cells appear to play an important role in DM pathogenesis and IFN-β production.