MicroRNA expression profiling identifies miR-31 and miR-485-3p as regulators in the pathogenesis of Discoid Cutaneous Lupus.

Cutaneous lupus erythematosus (CLE) is a common and disfiguring manifestation in systemic lupus erythematosus (SLE). Subacute-cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE) are the most prevalent forms. Despite sharing histological similarities, clinically they differ in their course and prognosis, suggesting different pathogenesis. Here, we show that DLE-affected skin has a specific microRNA expression profile when compared with SCLE. Among the DLE-specific microRNAs, we identified one keratinocyte-derived microRNA, miR-31, and one leukocyte-derived microRNA, miR-485-3p. We show that UV and TGF-β1 stimulation up-regulates miR31 expression in DLE. Specific miR-31 overexpression induces keratinocyte apoptosis and NF-κB pathway activation with the production of related inflammatory cytokines; and contributes to the recruitment of neutrophils and intermediate monocytes at the inflammation site. IL-1α and TGF-β1 stimulation increases the expression of miR-485-3p in peripheral mononuclear blood cells from DLE patients and induced T cell activation, mainly of CD8 lymphocytes. In addition, miR-485-3p overexpression in dermal fibroblasts contributes to fibrosis by targeting peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Collectively, our findings suggest that overexpression of miR-31 and miR-485-p contribute to skin inflammation in DLE lesions by regulating the production of inflammatory mediators and attracting neutrophils and intermediate monocytes to the skin.