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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1522076
This article is part of the Research Topic Single Cell Technologies for the Interrogation of Immunological Disease Mechanisms View all 9 articles
Single-cell RNA-seq reveals immune cell heterogeneity and increased Th17 cells in human fibrotic skin diseases
Provisionally accepted- Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Background: Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. The immune cells are postulated to exert a pivotal role in the development of fibrotic skin disease. Single-cell RNA sequencing has been reported to be used to explore the composition and functionality of immune cells present in fibrotic skin diseases. However, these studies detected the gene expression of all cells in fibrotic skin diseases and didn't enrich immune cells. Thus, the precise immune cell atlas in fibrotic skin diseases remains unknown. In this study, we plan to investigate the intricate cellular landscape of immune cells in keloid, a paradigm of fibrotic skin diseases.Methods: CD45 + immune cells were enriched by fluorescence activated cell sorting. Single-cell RNAsequencing was used to analyze the cellular landscape of immune cells in keloid and normal scar tissues. Ki-67 staining, scratch experiment, real-time PCR and western blot were used to explore the functions of Th17 cell supernatant on keloid fibroblasts.Results: Our findings revealed the intricate cellular landscape of immune cells in fibrotic skin diseases. We found that the percentage of Th17 cells was significantly increased in keloid compared to normal scar. All subclusters of macrophages and DCs showed similar proportions between keloid samples and normal scar samples. However, up-regulated genes in keloid M1 macrophages, M2 macrophages and cDC2 are associated with MHC class II protein complex assembly and antigen assembly, indicating that macrophages and cDC2 are active in keloid. Functional studies suggested that the supernatant of Th17 cell could promote proliferation, collagen expression and migration of keloid fibroblasts through IL-17A. Importantly, increased Th17 cells are also found in other fibrotic skin diseases hypertrophic scar and scleroderma, suggesting this represents a broad mechanism for skin fibrosis.In summary, we built a single-cell atlas of fibrotic skin diseases in this study. In addition, we explored the function of Th17 cells-fibroblast interaction on skin fibrosis. These findings will help to understand fibrotic skin disease pathogenesis in depth and identify potential targets for fibrotic skin disease treatment.
Keywords: immune cell, Th17 cell, Fibrotic skin diseases, Keloid, macrophage, dendritic cell, IL-17
Received: 03 Nov 2024; Accepted: 16 Dec 2024.
Copyright: © 2024 Deng, Xu, Zhang, Liu, Wang, Chen, Yao, Zhu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xue-Yan Xu, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Long-Can Liu, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Xuan Wang, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Jun-Yi Chen, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Liu-Yi Yao, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Ding-Heng Zhu, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
Bin Yang, Dermatology Hospital of Southern Medical University, Guangzhou,Guangdong, China
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