Zhang Wei, Zhang Jiayu, Jiao Dian, Tang Qisheng, Gao Xiaoping, Li Zhenyu, Yang Fa, Zhao Zhiguang, Yang Longfei
Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, People's Republic of China.
Department of Urology, Air Force Hospital of Southern Theater Command, Guangzhou, Guangdong, 510062, People's Republic of China.
J Inflamm Res. 2024 Aug 13;17:5327-5346. doi: 10.2147/JIR.S466317. eCollection 2024.
Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear.
In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results.
Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell-cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor-ligand pair.
Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD.
硬化性苔藓型尿道狭窄疾病（LS USD）是一种难治性进展性疾病，主要影响男性前尿道。已提出多种潜在病因，如遗传、自身免疫、感染以及接触感染性尿液等。然而，男性尿道LS的确切病因仍不清楚。
在本研究中，我们进行了单细胞RNA测序，以确定3例LS USD患者和3例非LS USD患者的转录谱。采用免疫荧光法确认单细胞测序结果。
我们的研究揭示了LS USD中静脉内皮细胞（ECs）、平滑肌细胞（SMCs）和成纤维细胞（FBs）的不同亚群比例较高，这些亚群促成了主要参与促炎和免疫反应的组织微环境。特别是，FBs表现出一个独特的亚群Fib7，它仅存在于LS USD中，并表现出较高水平的SAA1和SAA2表达。巨噬细胞的积累以及M1/M2样表型巨噬细胞比例失调可能参与了LS USD的发病机制。通过细胞间通讯分析，我们确定了LS USD中涉及CXCL8/ACKR1和CCR7/CCL19的显著相互作用。值得注意的是，Fib7通过SAA1/FPR2受体-配体对与IL-1B巨噬细胞表现出独特的通讯。
我们的研究为LS USD的组织微环境提供了深入了解，这可能对理解LS USD的发病机制具有重要价值。
