<i>CYP2S1</i> might regulate proliferation and immune response of keratinocyte in psoriasis

Psoriasis is an autoimmune skin disorder influenced by genetic, epigenetic and environmental factors. We previously found <i>CYP2S1</i> intragenic DNA methylation cg19430423 site strongly hypomethylated in psoriatic skin tissues. In this study, we performed methylation loci fine-mapping to search the top signals in the entire <i>CYP2S1</i> gene region, and further carried out gene expression assay, cell proliferation, apoptosis, differentiation and migration in <i>CYP2S1</i> overexpressed (<i>CYP2S1</i>^over) and silenced (siRNA) human keratinocytes. Target bisulphite conversion sequencing revealed cg19430423 and nearby two loci were the top differentially methylated loci. These three loci located within active enhancer region marked by H3K4Me1 and H3K27AC peaks. Cg19430423 might not bind with ATF1 directly. <i>CYP2S1</i>^over repressed NHEK cell proliferation, but have no confirmed evidence on affecting migration, apoptosis and differentiation. Real-time PCR showed that <i>CYP2S1</i> inhibited expression of <i>IL1β, IL8, IL33, IL36, LL37, CXCL10</i> and <i>CCL20</i> gene. In summary, <i>CYP2S1</i> might inhibit keratinocyte proliferation, and modulate immune response through <i>IL-8, IL-33, IL-36, CXCL-10, CCL20</i>, thus contribute to the development of psoriasis.