MicroRNAs (miRNAs) are small RNAs which are potent regulators of gene expression and have been implicated in the regulation of inflammatory responses and psoriasis. Psoriasis is a chronic inflammatory skin disease characterized by a disturbed interplay between immune cells and keratinocytes maintaining a vicious circle of inflammation. Previously, we identified miR-149 as a miRNA significantly suppressed in keratinocytes in psoriasis skin lesions and showed that IFN-γ suppresses miR-149-expression in keratinocytes. Moreover, we found that miR-149 mediates the cross-talk between the IFN-γ and the TWEAK pathways in keratinocytes in psoriasis. To better understand the role of miR-149 in skin biology and in inflammatory skin diseases, we have generated mice with keratinocyte-specific deletion of miR-149 (miR-149 EKO mice). MiR-149 EKO mice are viable and display a normal skin phenotype. However, upon topical application of the TLR7-agonist imiquimod, miR-149 EKO mice develop more severe psoriasis-like skin inflammation with increased epidermal thickness, increased keratinocyte proliferation, and significantly higher expression of inflammatory mediators as compared to wild type animals. Moreover, an increased number of infiltrating immune cells was observed the imiquimod-treated skin of miR-149 EKO mice as compared to wild-type controls. Altogether, our results suggest that miR-149 acts as a break on keratinocyte inflammatory responses under homeostatic conditions and its suppression in psoriasis is part of the pathogenic circuits sustaining skin inflammation.

ESDR346 - MiR-149: a microRNA regulating keratinocyte immune responses in psoriasis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.