Integrative bioinformatic analysis identified IFIT3 as a novel regulatory factor in psoriasis

J Cell Biochem. 2022 Sep 28. doi: 10.1002/jcb.30332. Online ahead of print.

Abstract

Psoriasis is an autoimmune skin disease with poor prognosis. Currently, there is no cure for psoriasis and the pathogenic mechanism of psoriasis remains unclear. Our study aims to explore key regulators underlying psoriasis and potential targets for psoriasis treatment. RNA-seq data of psoriasis and normal tissues were extracted from Gene Expression Omnibus database to screen differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) was conducted to identify key gene modules correlated with psoriasis. Enrichment analysis was used to characterize identified genes. The expression of identified genes was verified in a data set with various types of psoriasis lesion tissues and six psoriasis and healthy control tissues by quantitative polymerase chain reaction and immunohistochemistry assays. And the biological functions of IFIT3 in keratinocytes were determined by colony formation assays, Cell Counting Kit-8, and enzyme-linked immunosorbent assays. A total of 594 overlapped genes (370 upregulated and 224 downregulated) were selected as DEGs between psoriasis and normal tissues in three independent data sets. These genes were enriched in interferon-related pathway and cytokine-related pathway. Weighted correlation network analysis identified several gene modules that were associated with psoriasis. Overlapped genes between gene modules and DEGs were associated with interferon-related pathway and T cell activities. Among these genes, OAS1, USP18, and IFIT3 had higher expression levels in psoriasis vulgaris (PV) and nonpustular palmoplantar psoriasis (NPPP) tissues but not Palmoplantar Pustular Psoriasis (PPPP). Meanwhile, these results were confirmed in our independent psoriasis tissue cohort. And results of in vitro experiments showed that inhibition of IFIT3 significantly impaired the proliferation capacity and CXCL1, CCL20, IL-1β, and IL-6 secretion of keratinocytes. Our study identified key genes and pathways underlying the pathogenesis of psoriasis through the conduct of integrated analysis. OAS1, USP18, and IFIT3 could be potential targets for the treatment of psoriasis. IFIT3 can promote the proliferation and immune activation of keratinocytes and facilitates the development of psoriasis.

Keywords: IFIT3; OAS1; USP18; WGCNA; psoriasis.