Table3_Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis.PDF

Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

特发性声门下狭窄（Idiopathic subglottic stenosis, ISGS）是一种病因未明的罕见上气管纤维化疾病。该病好发于成年白人女性患者，因进行性瘢痕形成与炎症反应引发严重气道狭窄，临床表现为呼吸困难、喘鸣及嗓音改变。内镜治疗后常易复发，而手术切除与重建则可获得优异的长期功能预后。本研究旨在通过单细胞RNA测序（single cell RNA sequencing）阐明目前尚未被认知的ISGS病理特征。我们的scRNAseq分析揭示了声门下瘢痕组织的细胞构成，包括存在病理性促纤维化成纤维细胞亚型，以及处于促纤维化状态的施万细胞 (Schwann cells)。此外，本研究还发现了与病理状态相关的浆细胞增多现象。通过扩展生物信息学分析，我们解析了细胞外基质 (extracellular matrix) 相关因子的病理变化。本研究数据证实ISGS中存在持续的纤维化进程，并为成纤维细胞、施万细胞及浆细胞在ISGS发病机制中的作用提供了全新的研究视角。该研究成果或将为ISGS的诊断与治疗新策略开发提供新思路。