TY - T1的单核吞噬细胞系统导致纤维化在移植后闭塞性脉管炎细支气管炎JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.00344 -2020欧元六世- 57 - 3 SP - 2000344 AU - Di Campli Maria-Pia盟——Azouz Abdulkader AU - Assabban,阿西娅盟——Scaillet杰西卡盟——Splittgerber马里恩·AU - Van Keymeulen,亚历山德拉·AU - Libert,弗雷德里克·AU - Remmelink,米利亚姆·AU - Le Moine,阿兰·AU - Lemaitre,菲利普·AU - Goriely,Stanislas Y1 - 2021/03/01 UR - //www.qdcxjkg.com/content/57/3/2000344.abstract N2 -闭塞性细支气管炎综合征(BOS)是一种纤维化疾病,是肺移植后高死亡率的主要原因。肌成纤维细胞是这一纤维化过程的主要影响者,但其起源仍有争议。这项工作的目的是确定负责移植后气道纤维闭塞的间充质细胞的前体。在异位气管移植模型中,谱系追踪工具被用来追踪或耗尽肌纤维母细胞的潜在来源。异体移植物通过组织学、共聚焦显微镜、流式细胞术或单细胞转录组分析进行分析。采用显微组织和共聚焦显微镜对BOS外植体进行评价。同种异体的肌成纤维细胞是受体来源的。当受体小鼠接受他克莫司治疗时,我们观察到罕见的上皮-间充质转化现象和供体来源的肌纤维母细胞整体增加(p=0.0467),但这些细胞的比例仍然很低(7%)。在阻塞的气道中,大多数肌成纤维细胞是由造血细胞,特别是单核吞噬细胞系统产生的。 Ablation of Cx3cR1+ cells decreased fibro-obliteration (p=0.0151) and myofibroblast accumulation (p=0.0020). Single-cell RNA sequencing revealed similarities between myeloid-derived cells from allografts and both murine and human samples of lung fibrosis. Finally, myofibroblasts expressing the macrophage marker CD68 were increased in BOS explants when compared to controls (14.4% versus 8.5%, p=0.0249).Recipient-derived myeloid progenitors represent a clinically relevant source of mesenchymal cells infiltrating the airways after allogeneic transplantation. Therapies targeting the mononuclear phagocyte system could improve long-term outcomes after lung transplantation.Bronchiolitis obliterans syndrome remains a major cause of mortality after lung transplantation. The mononuclear phagocyte system actively contributes to fibrotic occlusion of rejected airways, thereby representing a promising novel therapeutic target. https://bit.ly/3hQh8UL ER -