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。

IF 3.5 4区 医学 Q1 DERMATOLOGY International Journal of Dermatology Pub Date : 2024-10-25 DOI:10.1111/ijd.17516
Daishi Li, Zhaohuai Li, Sitao Liu, Xiaozhen Chen, Xuanlin Che, Guangtong Deng, Jialing Chen, He Li, Rong Wang, Xiang Chen, Wenru Su, Juan Su
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引用次数: 0

摘要

背景:瘢痕疙瘩以异常的伤口愈合过程和高度复杂的免疫微环境为特征,给临床治疗带来了巨大挑战。成纤维细胞和血管内皮细胞(VEC)被认为是瘢痕疙瘩形成的主要细胞。然而,它们在瘢痕疙瘩免疫环境中的作用尚未得到彻底阐明:为了探索瘢痕疙瘩免疫景观中细胞的功能状态,我们对三个瘢痕疙瘩病变组织和两个健康皮肤标本进行了单细胞 RNA 测序分析。我们同时利用公共数据库中的瘢痕疙瘩数据进行外部验证:结果:与正常皮肤相比,病变皮肤中的特定亚群,如促炎性成纤维细胞(piF)和VEC明显升高。随后的差异基因表达和基因本体分析表明,这些亚群可能参与了微环境的形成。在瘢痕疙瘩中,免疫相关基因(P)的表达增加:我们的研究首次强调了 piF 和 VEC 在瘢痕疙瘩免疫微环境中的作用,为治疗开发提供了潜在靶点。
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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.

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来源期刊
CiteScore
4.70
自引率
2.80%
发文量
476
审稿时长
3 months
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.
期刊最新文献
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