Daishi Li, Zhaohuai Li, Sitao Liu, Xiaozhen Chen, Xuanlin Che, Guangtong Deng, Jialing Chen, He Li, Rong Wang, Xiang Chen, Wenru Su, Juan Su
{"title":"单细胞 RNA 测序突显了促炎性成纤维细胞、血管内皮细胞和免疫细胞在瘢痕疙瘩免疫微环境中的作用。","authors":"Daishi Li, Zhaohuai Li, Sitao Liu, Xiaozhen Chen, Xuanlin Che, Guangtong Deng, Jialing Chen, He Li, Rong Wang, Xiang Chen, Wenru Su, Juan Su","doi":"10.1111/ijd.17516","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Keloids, characterized by an aberrant wound-healing process and a highly complex immune microenvironment, pose significant challenges for clinical management. Fibroblasts and vascular endothelial cells (VEC) were identified as the leading cells of keloid development. However, their roles in the keloid immune landscape have yet to be thoroughly elucidated.</p><p><strong>Methods: </strong>To explore the functional state of cells in the immune landscape of keloids, we conducted a single-cell RNA sequencing analysis on the tissue from three keloid lesions and two specimens of healthy skin. We simultaneously utilized available keloid data from the public database for external validation.</p><p><strong>Results: </strong>Specific subsets, such as proinflammatory fibroblasts (piF) and VEC, were markedly elevated in lesional skin compared to normal skin. Subsequent differential gene expression and Gene Ontology analyses indicated that these subsets may be involved in shaping the microenvironment. In keloids, there is an increased expression of immune-associated genes (P < 0.05), including TNFRSF6B, HGF, and TGFB3, alongside a decreased expression of inflammatory chemokines in the piF. Moreover, the significant upregulation of immune suppressive genes (P < 0.05), including CD39, CD73, and HIF1A, suggested the potential involvement of VEC as a conditional immune subpopulation in the keloid microenvironment. Immune cell communication analysis revealed preferential enrichment of macrophages and Tregs, highlighting intensified macrophage-centered interactions within the keloid microenvironment.</p><p><strong>Conclusion: </strong>Our study highlighted the role of piF and VEC in the immune microenvironment of keloids for the first time, providing potential targets for therapeutic development.</p>","PeriodicalId":13950,"journal":{"name":"International Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Single-cell RNA sequencing highlights the role of proinflammatory fibroblasts, vascular endothelial cells, and immune cells in the keloid immune microenvironment.\",\"authors\":\"Daishi Li, Zhaohuai Li, Sitao Liu, Xiaozhen Chen, Xuanlin Che, Guangtong Deng, Jialing Chen, He Li, Rong Wang, Xiang Chen, Wenru Su, Juan Su\",\"doi\":\"10.1111/ijd.17516\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Keloids, characterized by an aberrant wound-healing process and a highly complex immune microenvironment, pose significant challenges for clinical management. Fibroblasts and vascular endothelial cells (VEC) were identified as the leading cells of keloid development. However, their roles in the keloid immune landscape have yet to be thoroughly elucidated.</p><p><strong>Methods: </strong>To explore the functional state of cells in the immune landscape of keloids, we conducted a single-cell RNA sequencing analysis on the tissue from three keloid lesions and two specimens of healthy skin. We simultaneously utilized available keloid data from the public database for external validation.</p><p><strong>Results: </strong>Specific subsets, such as proinflammatory fibroblasts (piF) and VEC, were markedly elevated in lesional skin compared to normal skin. Subsequent differential gene expression and Gene Ontology analyses indicated that these subsets may be involved in shaping the microenvironment. In keloids, there is an increased expression of immune-associated genes (P < 0.05), including TNFRSF6B, HGF, and TGFB3, alongside a decreased expression of inflammatory chemokines in the piF. Moreover, the significant upregulation of immune suppressive genes (P < 0.05), including CD39, CD73, and HIF1A, suggested the potential involvement of VEC as a conditional immune subpopulation in the keloid microenvironment. Immune cell communication analysis revealed preferential enrichment of macrophages and Tregs, highlighting intensified macrophage-centered interactions within the keloid microenvironment.</p><p><strong>Conclusion: </strong>Our study highlighted the role of piF and VEC in the immune microenvironment of keloids for the first time, providing potential targets for therapeutic development.</p>\",\"PeriodicalId\":13950,\"journal\":{\"name\":\"International Journal of Dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/ijd.17516\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ijd.17516","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Single-cell RNA sequencing highlights the role of proinflammatory fibroblasts, vascular endothelial cells, and immune cells in the keloid immune microenvironment.
Background: Keloids, characterized by an aberrant wound-healing process and a highly complex immune microenvironment, pose significant challenges for clinical management. Fibroblasts and vascular endothelial cells (VEC) were identified as the leading cells of keloid development. However, their roles in the keloid immune landscape have yet to be thoroughly elucidated.
Methods: To explore the functional state of cells in the immune landscape of keloids, we conducted a single-cell RNA sequencing analysis on the tissue from three keloid lesions and two specimens of healthy skin. We simultaneously utilized available keloid data from the public database for external validation.
Results: Specific subsets, such as proinflammatory fibroblasts (piF) and VEC, were markedly elevated in lesional skin compared to normal skin. Subsequent differential gene expression and Gene Ontology analyses indicated that these subsets may be involved in shaping the microenvironment. In keloids, there is an increased expression of immune-associated genes (P < 0.05), including TNFRSF6B, HGF, and TGFB3, alongside a decreased expression of inflammatory chemokines in the piF. Moreover, the significant upregulation of immune suppressive genes (P < 0.05), including CD39, CD73, and HIF1A, suggested the potential involvement of VEC as a conditional immune subpopulation in the keloid microenvironment. Immune cell communication analysis revealed preferential enrichment of macrophages and Tregs, highlighting intensified macrophage-centered interactions within the keloid microenvironment.
Conclusion: Our study highlighted the role of piF and VEC in the immune microenvironment of keloids for the first time, providing potential targets for therapeutic development.
期刊介绍:
Published monthly, the International Journal of Dermatology is specifically designed to provide dermatologists around the world with a regular, up-to-date source of information on all aspects of the diagnosis and management of skin diseases. Accepted articles regularly cover clinical trials; education; morphology; pharmacology and therapeutics; case reports, and reviews. Additional features include tropical medical reports, news, correspondence, proceedings and transactions, and education.
The International Journal of Dermatology is guided by a distinguished, international editorial board and emphasizes a global approach to continuing medical education for physicians and other providers of health care with a specific interest in problems relating to the skin.