Topical administration of nanocarrier miRNA-210 antisense ameliorates imiquimod-induced psoriasis-like dermatitis in mice.

Abstract

Psoriasis is a chronic, recurrent inflammatory autoimmune skin disease. Although its etiology and pathogenesis are complex and multifarious, it has been proved to be closely related to dysregulation of immune cell function as well as keratinocyte proliferation/differentiation. Our previous study demonstrated that miRNA-210 (miR-210) plays an important role in the formation of skin lesions and immune imbalance in psoriasis. Here, we developed a biomimetic reconstituted high-density lipoprotein (rHDL) nanocarrier gel containing miR-210 antisense (NG-anti-miR-210) to investigate its effect on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. We found that topical treatment with NG-anti-miR-210 significantly decreased the expression of miR-210 in both the skin lesions and splenic CD4+ T cells from IMQ-induced psoriasis-like mouse models and ameliorated the dermatitis in terms of the erythema, scales, acanthosis and dermal inflammatory cell infiltration in IMQ-induced mice. In addition, the proportion of T-helper (Th)1 and Th17 cells in dermal and splenic cells of IMQ-treated mice were decreased by application of NG-anti-miR-210, accompanied by decreased interleukin-17A and γ-interferon mRNA levels. Therefore, our data demonstrate that topical inhibition of miR-210 delivered by rHDL nanocarrier effectively alleviates the psoriasis-like inflammation in mice and provides a potentially effective topical drug for psoriasis.