L36G is associated with cutaneous antiviral competence in psoriasis.

Background: Psoriasis is a common inflammatory skin disease that has a great impact on patients' physical and mental health. However, the causes and underlying molecular mechanisms of psoriasis are still largely unknown. Methods: The expression profiles of genes from psoriatic lesion samples and skin samples from healthy controls were integrated Results: We identified 148 DEGs between psoriatic and healthy samples. GO and KEGG pathway enrichment analysis suggested that DEGs are mainly involved in the defense response to other organisms. The PPI network showed that 11 antiviral proteins (AVPs) were hub genes. scGSEA analysis in the single-cell transcriptome dataset showed that those hub genes are highly expressed in keratinocytes, especially in suprabasal keratinocytes. ISG15, MX1, IFI44L, and IFI27 were the characteristic genes of psoriasis in suprabasal keratinocytes. scWGCNA showed that three cytokines-IL36G, MIF, and IL17RA-were co-expressed in the turquoise module. Only interleukin-36 gamma (IL36G) was positively correlated with AVPs in the integrated dataset. IL36G and AVPs were found co-expressed in a substantial number of suprabasal keratinocytes. Furthermore, we found that the expression levels of IL36G and the 4 AVPs showed positive correlation with PASI score in patients with psoriasis, and that these levels decreased significantly during treatment with biological therapies, but not with methotrexate. Conclusion: IL36G and antiviral proteins may be closely related with the pathogenesis of psoriasis, and they may represent new candidate molecular markers for the occurrence and severity of psoriasis.