IL-36 signaling in keratinocytes controls early IL-23 production in Aldara®-induced skin inflammation in mice

IL-36R signaling plays an important role in the pathogenesis of psoriasis. We ought to assess the specific function of IL-36R in keratinocytes for the pathology of Aldara®-induced psoriasis-like skin inflammation. Il36r-/- (KO) and Il36rΔK (DK) mice as well as their littermate controls, respectively Il36r+/+ (WT) and Il36rfl/fl (FL) mice, were challenged with the topical application of Aldara® on one ear during 3 or 7 days. RNASeq was performed on treated (AL) and untreated (CT) ears. Fold change analysis combined with RPKM and RT-qPCR allowed us to identify genes which were specifically regulated by IL-36R signaling in keratinocytes during the course of the treatment. We notably demonstrated that both IL-23 subunits (Il23a and Il12b) fell into this category. Skin mRNA profiles from WT, KO, FL and DK mice in AL and CT ears at days 3 and 7 of Aldara treatment (4-6 replicates per condition) were generated using TruSeq mRNA stranded kit on an Illumina HiSeq 4000 sequencer.