Single-Cell Profiling Unveils the Inflammatory Heterogeneity within Cutaneous Lesions of Bullous Pemphigoid

大疱性类天疱疮 医学 仿形(计算机编程) 皮肤病科 类天疱疮 免疫学 抗体 计算机科学 操作系统
作者
Yue Ruan,Chuqiao Xu,Tianyu Zhang,Zhu Lin,Hailun Wang,Jingying Wang,Haiqin Zhu,Chuanxin Huang,Meng Pan
出处
期刊:Journal of Investigative Dermatology [Elsevier BV]
卷期号:144 (10): 2176-2186.e6 被引量:6
标识
DOI:10.1016/j.jid.2024.02.029
摘要

Bullous pemphigoid (BP) is a subepidermal blistering skin disease with a complex pathogenesis involving various immune cells. However, the transcriptional features of these cells remain poorly defined. Here, we construct a comprehensive and single-cell resolution atlas of various immune cells within BP skin lesions via integrative single-cell analysis, flow cytometry and multiplex immunohistochemistry. We observed prominent expansion and transcriptional changes in mast cells, macrophages, basophils, and neutrophils within BP lesions. Mast cells within the lesions adopted an active state and exhibited an elevated capacity for producing pro-inflammatory mediators. We observed an imbalance of macrophages/dendritic cells within BP lesions. Two macrophage subpopulations (NLRP3+ and C1q+) with distinct transcriptional profiles were identified and up-regulated effector programs. T peripheral helper (Tph)-like Th2 cells were expanded in skin lesions and peripheral blood of BP patients and were capable of promoting B cell responses. Additionally, we observed clonally expanded GZMB+ CD8+ T cells within BP lesions. Chemokine-receptor mapping revealed the potential roles of macrophages and mast cells in recruiting pathogenic immune cells and underlying mechanisms within BP lesions. Thus, this study reveals key immune-pathogenic features of BP lesions, thereby providing valuable insights for potential therapeutic interventions in this disease.
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