Single-cell transcriptomics reveals aberrant skin-resident cell populations and identifies fibroblasts as a determinant in rosacea

• Published in: Nature communications Vol. 15; no. 1; pp. 8737 - 16
• Main Authors: Chen, Mengting, Yang, Li, Zhou, Peijie, Jin, Suoqin, Wu, Zheng, Tan, Zixin, Xiao, Wenqin, Xu, San, Zhu, Yan, Wang, Mei, Jian, Dan, Liu, Fangfen, Tang, Yan, Zhao, Zhixiang, Huang, Yingxue, Shi, Wei, Xie, Hongfu, Nie, Qing, Wang, Ben, Deng, Zhili, Li, Ji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-10-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 42/89; 49/91; 631/80/304; 64/60; 692/4017; 692/420/256/2515; 692/699/249/2510; 82/51; Adult; Animals; Cell activation; Damage; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Fibroblasts; Fibroblasts - metabolism; Humanities and Social Sciences; Humans; Immunological memory; Interferon-gamma - metabolism; Keratinocytes; Keratinocytes - metabolism; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Macrophages - metabolism; Memory cells; Mice; Mice, Inbred C57BL; Molecular modelling; multidisciplinary; Muscle contraction; Muscular function; Phenotypes; Population studies; Populations; Rosacea; Rosacea - genetics; Rosacea - immunology; Rosacea - pathology; Schwann Cells - metabolism; Schwann Cells - pathology; Science; Science (multidisciplinary); Single-Cell Analysis; Skin - immunology; Skin - metabolism; Skin - pathology; Skin diseases; Transcriptome; Transcriptomics; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52946-7

Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.
Rosacea is a common chronic inflammatory skin disorder mainly affecting the central face. Here, a single-cell atlas of facial skin from rosacea patients and healthy individuals reveals the molecular and cellular changes in skin-resident cell populations and identifies fibroblasts as a determinant in rosacea development.