Epidermal keratinocytes from psoriatic resolved skin keep disease residual transcriptomic and epigenomic profiles

We aimed to compare resolved vs. never lesional psoriatic skin epidermal keratinocytes to identify transcriptomic and epigenomic differences, which may contribute to the local relapse in clinically healed skin. We applied high-throughput RNA sequencing on the epidermal compartment to obtain global transcriptome data. Visualization of the general pattern of 5-mC (5-methylcytosine) and 5-hmC (5-hydroxymethylcytosine) epigenetic marks was performed using immunofluorescence staining. We also examined the overlap between our study's resolved vs. never lesional differentially expressed genes (DEGs) and the lesional vs. healthy epidermis DEGs from available datasets. We identified SAMHD1, C10orf99, and AKR1B10 transcripts as strongly dysregulated genes in the resolved epidermis, which are well-known to be involved in psoriasis pathogenesis. The 102 overlapping genes were enriched in WNT, TNF, and mTOR signaling pathways. We observed decreased intensity of 5-mC and 5-hmC in resolved vs. never lesional epidermis. The 5-hmC decreased content was accompanied by diminished Ten-eleven translocation (TET) 3 mRNA expression. Our findings suggest that disease residual epigenomic and transcriptomic profiles persist in resolved epidermal keratinocytes and may grant a site-specific flare-up in resolved vs. never lesional skin.