Atypical chemokine receptor 1-positive endothelial cells mediate leucocyte infiltration and synergize with secreted frizzled-related protein 2/asporin-positive fibroblasts to promote skin fibrosis in systemic sclerosis

作者：Yan Huang, Weilin Pu, Lei Wang, Qianqian Ma, Yanyun Ma, Qingmei Liu, Shuai Jiang, Xiangyue Zhao, Yuting Zhang, Qiuyu He, Yulong Tang, Jing Liu, Jui‐Ming Lin, Xiangguang Shi, Wenzhen Tu, Yuanyuan Chen, Jinran Lin, Yiyi Gong, Wenyu Wu, Jiucun Wang · 发表于：British Journal of Dermatology · 年份：2024 · DOI：10.1093/bjd/ljae286 · 被引用次数：20 · 研究领域：Systemic Sclerosis and Related Diseases、Inflammatory Myopathies and Dermatomyositis、Multiple Sclerosis Research Studies

BACKGROUND: Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis. OBJECTIVES: To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem. METHODS: Single-cell RNA sequencing was performed on skin biopsies from three healthy donors and seven patients with SSc. Additional data from three patients with localized scleroderma available in the Gene Expression Omnibus (GSE160536) were integrated by Harmony. CellChat (version 1.5.0) was used to analyse the cell communication network. A Transwell® assay and a bleomycin (BLM) mouse model were used to explore the role of atypical chemokine receptor 1 (ACKR1; 'Duffy antigen') in immune cell infiltration. Milo single-cell Western blot was used to show fibroblast subcluster activation. RESULTS: A total of 62 295 cells were obtained and subpopulations of stromal and immune cells identified. Interaction network analysis found that multiple chemokines secreted by macrophages, pericytes and proinflammatory fibroblasts could ...