Identifying TNFSF4low-MSCs superiorly treating idiopathic pulmonary fibrosis through Tregs differentiation modulation

作者：Yuanyuan Xie, Qing Yi, Congwang Xu, Yaping Wang, Yue Jiang, Yirui Feng, Liudi Wang, Hui Yang, Yingwei Zhang, Bin Wang · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04313-6 · 被引用次数：5 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、IL-33, ST2, and ILC Pathways、Systemic Sclerosis and Related Diseases

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive lung disorder, presenting clinically with symptoms such as shortness of breath and hypoxemia. Despite its severe prognosis and limited treatment options, the pathogenesis of idiopathic pulmonary fibrosis remains poorly understood. This study aims to investigate the therapeutic potential of mesenchymal stromal cells in treating idiopathic pulmonary fibrosis, focusing on their ability to modulate regulatory T cells through the low tumor necrosis factor superfamily member 4 (TNFSF4) pathway. The goal is to identify mesenchymal stromal cells subtypes with optimal immunomodulatory effects to enhance regulatory T cells functions and ameliorate fibrosis. METHODS: We identified the immune characteristics of idiopathic pulmonary fibrosis by mining and analyzing multiple public datasets and detecting regulatory T cells in the blood and lung tissues of idiopathic pulmonary fibrosis patients. An extensive examination followed, including assessing the impact of mesenchymal stromal cells on regulatory T cells proportions in peripheral blood and lung tissue, and exploring the specific role of TNFSF4 expression in regulatory T cells modulation. Whole-genome sequencing and cluster analysis were used to identify mesenchymal stromal cells subtypes with low TNFSF4 expression. RESULTS: -MSCs) demonstrated enhanced ability to regulate regulatory T cells subpopulations and exhibited pronounced anti-fibrotic effects in the bleomycin-induced ...