肌成纤维细胞
生物
成纤维细胞
免疫系统
炎症
纤维化
细胞生物学
重编程
癌症研究
心脏纤维化
细胞
免疫学
病理
细胞培养
医学
遗传学
作者
Jamila H. Siamwala,F. Pagano,Patrycja M. Dubielecka,Malina J. Ivey,José P. Guirao-Abad,Alexander Zhao,Sonja Chen,Haley Granston,Jae Yun Jeong,Sharon Rounds,Onur Kanisicak,Sakthivel Sadayappan,Richard J. Gilbert
标识
DOI:10.1038/s42003-023-05463-0
摘要
Abstract The source and roles of fibroblasts and T-cells during maladaptive remodeling and myocardial fibrosis in the setting of pulmonary arterial hypertension (PAH) have been long debated. We demonstrate, using single-cell mass cytometry, a subpopulation of endogenous human cardiac fibroblasts expressing increased levels of CD4, a helper T-cell marker, in addition to myofibroblast markers distributed in human fibrotic RV tissue, interstitial and perivascular lesions in SUGEN/Hypoxia (SuHx) rats, and fibroblasts labeled with pdgfrα CreERt2/+ in R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor expression, modifies the secretome, and differentiates cardiac fibroblasts to form CD68-positive cell clusters. IL-1β also activates stemness markers, such as NANOG and SOX2, and genes involved in dedifferentiation, lymphoid cell function and metabolic reprogramming. IL-1β induction of lineage traced primary mouse cardiac fibroblasts causes these cells to lose their fibroblast identity and acquire an immune phenotype. Our results identify IL-1β induced immune-competency in human cardiac fibroblasts and suggest that fibroblast secretome modulation may constitute a therapeutic approach to PAH and other diseases typified by inflammation and fibrotic remodeling.
科研通智能强力驱动
Strongly Powered by AbleSci AI