The PRINS lncRNA is a differentially expressed transcript in psoriatic perilesional epidermis. We have recently shown its role in keratinocytes’ inflammatory responses by downregulating the expression of IL-6 and CCL-5 through sequence specific binding to their respective mRNAs. We aimed at identifying additional targets for PRINS-mediated regulation in inflammatory reactions of normal human epidermal keratinocytes (NHEK; n=4). Cytosolic exposure to synthetic analogues of dsDNA [poly(dA:dT)] and dsRNA [poly(I:C)] was used to model psoriasis-associated inflammatory conditions with plasmid-based overexpression or silencing of PRINS. Expression of inflammatory molecules was studied by a real-time RT-PCR-array. Out of 84 studied inflammatory genes 37 and 46 were upregulated in response to the different nucleic acid treatments, including IL23-A, a cytokine playing an important role in psoriasis pathogenesis. Overexpression of PRINS resulted in reduced response of IL-23A expression to nucleic acid induction, but silencing had an opposite effect. In silico analysis revealed two potential interaction sites of PRINS for the IL-23A mRNA, overlapping with the previously described IL-6 interacting site. We observed high intra-individual differences among the NHEK cultures upon PRINS overexpression suggesting the involvement of genetic variants on the polymorphic IL-23A gene. However, we could not identify any IL-23A variants correlating with IL-23A expression-rate, but we noticed a certain threshold of IL-23A expression to be reached for its effective downregulation by PRINS. We propose that PRINS acts as a fine-tuner of inflammatory gene expression in keratinocytes through different lncRNA–mRNA interactions, and altered PRINS expression in psoriatic perilesional epidermis contributes to disease pathogenesis.

ESDR207 - PRINS long non-coding RNA regulates IL-23 expression of keratinocytes

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING