纤维化
特雷姆2
发病机制
病理
人体皮肤
医学
基因剔除小鼠
巨噬细胞
生物
癌症研究
免疫学
受体
免疫系统
遗传学
体外
髓系细胞
作者
Yunsheng Liang,Yongfei Hu,Jun Zhang,Huan Song,Xiaoqian Zhang,Yishan Chen,Peng Yu,Lei Sun,Yuzhe Sun,Ruzeng Xue,Suyun Ji,Chuanwei Li,Zhili Rong,Bin Yang,Yuping Xu
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2024-01-01
卷期号:14 (5): 2232-2245
摘要
Rationale: Systemic sclerosis (SSc) is a chronic and incurable autoimmune disease with high mortality rates, and skin fibrosis is one of distinguishing hallmarks in the pathogenesis. However, macrophage heterogeneity regulating skin fibrosis remain largely unknown. Methods: We established mouse disease model and performed single-cell RNA-sequencing (scRNA-seq) to resolve the dynamic and heterogenous characteristics of macrophages in skin fibrosis, and the role of TREM2-dependent macrophages in the pathological process was investigated using knockout mice and intraperitoneal transferring TREM2+ macrophages combining with functional assays. Results: We show that TREM2-expressing macrophages (TREM2+ MФs) accumulate in injured skin of mice treated by bleomycin (BLM) and human SSc, and their gene signatures and functional pathways are identified in the course of disease. Genetic ablation of Trem2 in mice globally accelerates and aggravates skin fibrosis, whereas transferring TREM2hi macrophages improves and alleviates skin fibrosis. Amazingly, we found that disease-associated TREM2+ MФs in skin fibrosis exhibit overlapping signatures with fetal skin counterparts in mice and human to maintain skin homeostasis, but each has merits in skin remodeling and development respectively. Conclusion: This study identifies that TREM2 acts as a functional molecule and a major signaling by which macrophage subpopulations play a protective role against fibrosis, and disease-associated TREM2+ MФs in skin fibrosis might undergo a fetal-like reprogramming similar to fetal skin counterparts.
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