Pyroptosis‐related gene signature elicits immune response in rosacea

Abstract

Rosacea is a complex chronic inflammatory skin disorder with high morbidity. Pyroptosis is known as a regulated inflammatory cell death. While its association with immune response to various inflammatory disorders is well established, little is known about its functional relevance of rosacea. So, we aimed to explore and enrich the pathogenesis involved in pyroptosis‐related rosacea aggravations. In this study, we evaluated the pyroptosis‐related patterns of rosacea by consensus clustering analysis of 45 ferroptosis‐related genes (FRGs), with multiple immune cell infiltration analysis to identify the pyroptosis‐mediated immune response in rosacea using GSE65914 dataset. The co–co‐work between PRGs and WGCNA‐revealed hub genes has established using PPI network. FRG signature was highlighted in rosacea using multi‐transcriptomic and experiment analysis. Based on this, three distinct pyroptosis‐related rosacea patterns (non/moderate/high) were identified, and the notably enriched pathways have revealed through GO, KEGG and GSEA analysis, especially immune‐related pathways. Also, the XCell/MCPcount/ssGSEA/Cibersort underlined the immune‐related signalling (NK cells, Monocyte, Neutrophil, Th2 cells, Macrophage), whose hub genes were identified through WGCNA (NOD2, MYD88, STAT1, HSPA4, CXCL8). Finally, we established a pyroptosis‐immune co‐work during the rosacea aggravations. FRGs may affect the progression of rosacea by regulating the immune cell infiltrations. In all, pyroptosis with its mediated immune cell infiltration is a critical factor during the development of rosacea.

Iron Metabolism of the Skin: Recycling versus Release

“…Additionally, the etiology of chronic wounds is critically regulated by iron and iron-dependent reactive oxygen species in fibroblasts and macrophages [ 102 ]. Furthermore, ferroptosis of various cell types is implicated in several skin diseases, such as vitiligo [ 103 ], melanoma [ 104 ] and rosacea [ 105 ], but whether it is indeed critical for the progression or control of these diseases remains to be tested.…”