伊利沙伯医院Christopher D. Buckley课题组的研究显示，不同类型的成纤维细胞亚群驱动不同的关节炎炎症和损伤。该项研究成果发表在2019年5月29日出版的《自然》上。

课题组人员确定和描述了不同的亚群成纤维细胞介导炎症或组织损伤的关节炎的生物学功能。该研究团队显示删除的成纤维细胞活化蛋白-α(FAPα)⁺成纤维细胞抑制炎症和骨侵蚀在小鼠的缓解和持久的关节炎的模型。单细胞转录分析发现FAPα⁺群中的两种不同的纤维母细胞亚群:FAPα⁺THY1⁺免疫效应成纤维细胞位于滑膜副线,和FAPα⁺THY1^-局限于滑膜衬里层的破坏性成纤维细胞。当过继转移到关节,FAPα⁺THY1^-成纤维细胞有选择性地介导骨和软骨损伤但对炎症影响较小,而FAPα⁺THY1⁺成纤维细胞的转移导致更严重和持续的炎症性关节炎,对骨骼和软骨影响最小。他们的发现描述了解剖学上离散的、功能上不同的、功能上不重叠的成纤维细胞亚群，对于旨在调节炎症和组织损伤的细胞治疗具有重要意义。

据悉，识别具有非重叠效应功能的淋巴细胞亚群对免疫介导性炎症疾病(IMIDs)靶向治疗的发展至关重要。然而，目前尚不清楚具有非重叠功能的成纤维细胞亚类是否也存在，并对类风湿性关节炎中观察到的多种组织驱动过程(如炎症和损伤)负责。

附：英文原文

Title: Distinct fibroblast subsets drive inflammation and damage in arthritis

Author:Adam P. Croft, Joana Campos, Kathrin Jansen, Jason D. Turner, Jennifer Marshall, Moustafa Attar, Loriane Savary, Corinna Wehmeyer, Amy J. Naylor, Samuel Kemble, Jenefa Begum, Kerstin Dürholz, Harris Perlman, Francesca Barone, Helen M. McGettrick, Douglas T. Fearon, Kevin Wei, Soumya Raychaudhuri, Ilya Korsunsky, Michael B. Brenner, Mark Coles, Stephen N. Sansom, Andrew Filer & Christopher D. Buckley

Issue&Volume:Volume 570 Issue 7760, 13 June 2019

Abstract: The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs)1,2. However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage3,4,5. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1 destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1 fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.

DOI: https://doi.org/10.1038/s41586-019-1263-7

Source: https://www.nature.com/articles/s41586-019-1263-7