343 Endogenous double-stranded RNA is a potential target for psoriasis therapy

The activation of endogenous double-stranded RNA (endo-dsRNA) signalling pathways is linked to a variety autoimmune diseases. Here, we investigated the role dsRNA in psoriasis by quantifying binding protein (DRBP) mRNA and mitochondrial formation response narrow-band UVB (NB-UVB) treatment. RNAseq data from 34 psoriatic patients treated with NB-UVB were analysed. Biopsies obtained four sites 24h after irradiation (lesional unirradiated, nonlesional unirradiated lesional irradiated one minimal erythemal dose (MED), three MEDs. Psoriatic skin had significantly higher expression all examined DRBP (RIG, MDA5, LGP2, PKR, OAS1-3, OASL) as compared (increase between 1.5-21.7 fold, p <0.001 for eight genes). treatment no effect on DRBPs or MEDs NB-UVB. Additionally, significant reduction (about 20%) transcripts was detected both doses(p-value 0.012 0.001, respectively). These results indicate that increased levels activate RIG, LGP2 skin. turn upregulate type1 IFN via recruiting TBK1, IRF3/7, which upregulated PKR binds endo-dsRNA, enhances IFN-α/β IRF3. Moreover, OASs trigger an antiviral RIG induced pathway. Once activated, strongly transcription thus creating vicious cycle exacerbates immune response. In conclusion, upregulation genes indicates endo-dsRNA may play crucial pathogenesis, early suggests important target therapy.