Single-cell RNA sequencing highlights the role of proinflammatory fibroblasts, vascular endothelial cells, and immune cells in the keloid immune microenvironment.

Autor: Li D; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China., Li Z; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China., Liu S; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China., Chen X; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China., Che X; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China., Deng G; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China., Chen J; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.; Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China., Li H; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China., Wang R; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China., Chen X; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China., Su W; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China., Su J; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China.; Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, China.; Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, China.; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Hu Nan Key Laboratory of Aging Biology, Changsha, China.
Jazyk: angličtina
Zdroj: International journal of dermatology [Int J Dermatol] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1111/ijd.17516
Abstrakt: 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.
(© 2024 the International Society of Dermatology.)
Databáze: MEDLINE
Externí odkaz: