英国格拉斯哥大学Mariola Kurowska-Stolarska和意大利杰美利大学医院基金会Stefano Alivernini课题组合作发现，类风湿关节炎（RA）患者不同滑膜组织巨噬细胞亚群调节炎症和症状缓解。相关论文发表在2020年6月29日出版的《自然-医学》杂志上。

目前，研究人员尚不清楚RA中无药物缓解的免疫调节机制。研究人员推测RA症状缓解过程中持续存在的滑膜组织巨噬细胞（STM）有助于关节稳态。使用单细胞转录组学分析了32,000个STM，研究人员鉴定了早期/活动性RA、难治性/活动性RA和症状持续缓解RA患者的表型变化。

在具有不同稳态、调节和炎症功能的四个STM亚群中，每种临床特征由九个离散表型簇的不同频率决定。将该细胞图谱与对滑膜活检荧光激活细胞分类STM进行的深表型、空间和功能分析相结合，研究人员揭示了两个STM亚群（MerTK^posTREM2^high和MerTK^posLYVE1^pos），其独特的缓解转录组特征丰富了炎症的负调控因子。

这些STM是消炎脂质介体的有效产生者，并在体外诱导滑膜成纤维细胞的修复反应。缓解率低的MerTK^pos STM与停止治疗后疾病复发风险增加相关。因此，针对MerTK^pos STM亚群的治疗可能是治疗RA的潜在策略。

附：英文原文

Title: Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis

Author: Stefano Alivernini, Lucy MacDonald, Aziza Elmesmari, Samuel Finlay, Barbara Tolusso, Maria Rita Gigante, Luca Petricca, Clara Di Mario, Laura Bui, Simone Perniola, Moustafa Attar, Marco Gessi, Anna Laura Fedele, Sabarinadh Chilaka, Domenico Somma, Stephen N. Sansom, Andrew Filer, Charles McSharry, Neal L. Millar, Kristina Kirschner, Alessandra Nerviani, Myles J. Lewis, Costantino Pitzalis, Andrew R. Clark, Gianfranco Ferraccioli, Irina Udalova, Christopher D. Buckley, Elisa Gremese, Iain B. McInnes, Thomas D. Otto, Mariola Kurowska-Stolarska

Issue&Volume: 2020-06-29

Abstract: Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterized by different frequencies of nine discrete phenotypic clusters within four distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas, combined with deep-phenotypic, spatial and functional analyses of synovial biopsy fluorescent activated cell sorted STMs, revealed two STM subpopulations (MerTKposTREM2high and MerTKposLYVE1pos) with unique remission transcriptomic signatures enriched in negative regulators of inflammation. These STMs were potent producers of inflammation-resolving lipid mediators and induced the repair response of synovial fibroblasts in vitro. A low proportion of MerTKpos STMs in remission was associated with increased risk of disease flare after treatment cessation. Therapeutic modulation of MerTKpos STM subpopulations could therefore be a potential treatment strategy for RA.

DOI: 10.1038/s41591-020-0939-8

Source: https://www.nature.com/articles/s41591-020-0939-8