969 Epidermis-specific deletion of miR-149 exacerbates psoriasis-like skin inflammation

MicroRNAs (miRNAs) are important regulators of gene expression and have been implicated in immunity inflammation. Chronic skin inflammation psoriasis is maintained by inflammatory circuits involving infiltrating immune cells keratinocytes. Recently we identified microRNA(miR)-149 to be suppressed keratinocytes showed that it acts as a link between IFN-g the TWEAK pathways. To further explore role miR-149 keratinocyte responses homeostasis, generated knockout mice with epidermis-specific deletion (miR-149 EKO). We report EKO viable display normal phenotype absence stimuli. However, isolated from responded stronger stimulation TWEAK. Induction psoriasiform topical application imiquimod (IMQ) led exacerbated compared control mice, increased epidermal thickness, infiltration skin, well higher psoriasis-associated mediators. RNA sequencing analysis IMQ-treated wild-type revealed an enrichment immune/inflammatory among differentially expressed genes animals. Similarly, intradermal injection IL-23 exacerbation vs. ear cell infiltration. Altogether, our results suggest downregulation amplifies enhancing responses.