AUTHOR=Li Yang , Li Min , Qu Caijie , Li Yongxi , Tang Zhanli , Zhou Zhike , Yu Zengzhao , Wang Xu , Xin Linlin , Shi Tongxin TITLE=The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.810290 DOI=10.3389/fimmu.2021.810290 ISSN=1664-3224 ABSTRACT=

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.