Cross-talk between IFN-? and TWEAK through miR-149 amplifies skin inflammation in psoriasis

BackgroundPsoriasis is a chronic inflammatory skin disease with disturbed interplay between immune cells and keratinocytes. A strong IFN-? signature characteristic for psoriasis skin, but the role of has been elusive. MicroRNAs are short RNAs regulating gene expression.ObjectiveOur aim was to investigate miR-149 in responses keratinocytes.MethodsmiR-149 expression measured by quantitative RT-PCR keratinocytes isolated from healthy lesional nonlesional skin. Synthetic injected intradermally into back mice, imiquimod applied induce psoriasis-like inflammation, which then evaluated at morphologic, histologic, molecular levels. transiently overexpressed or inhibited combination IFN-?- and/or TNF-related weak inducer apoptosis (TWEAK)-treatment.ResultsHere we report microRNA-mediated mechanism primes stimuli. Treatment results rapid long-lasting suppression Depletion leads widespread transcriptomic changes induction mediators enrichment TWEAK pathway. We show that IFN-?–mediated amplified TWEAK. receptor (TWEAKR/Fn14) identified as novel direct target miR-149. The vivo relevance this pathway supported decreased keratinocytes, well protective effect synthetic imiquimod-induced mouse model psoriasis.ConclusionOur data define new mechanism, TWEAK-induced through miR-149, promoting inflammation. Psoriasis expression. Our (TWEAK)-treatment. Here psoriasis.