德国埃尔朗根-纽伦堡大学Erhard Krnke小组取得一项新突破。他们发现滑膜组织中具有自我更新能力的巨噬细胞为关节提供了保护屏障。 相关论文发表于2019年8月29日出版的《自然》杂志。

研究人员使用fate-mapping结合三维激光片层扫描显微镜和单细胞RNA测序的方法，对健康人以及关节炎病人体内巨噬细胞亚群的组成、起源和分化进行全面的时空分析，并研究这些巨噬细胞在关节炎中的作用。研究人员发现，由不同的组织内源性CX3CR1⁺巨噬细胞群组成的动态膜样结构在滑膜衬里形成内源免疫屏障并隔离关节。这些形成屏障的巨噬细胞具有上皮细胞特有的特征，并通过嵌入滑膜组织的局部增殖的CX3CR1^-单核细胞库来维持它们的数量。单核细胞衍生形成的巨噬细胞促进关节炎症，与招募的单核细胞衍生而成的巨噬细胞不同，这些上皮样CX3CR1⁺内源巨噬细胞通过形成关节内部结构紧密的屏障来限制炎症反应。

该研究揭示了滑膜中巨噬细胞功能的多样性，并且对理解巨噬细胞在健康人和疾病中的作用具有重要意义。

研究人员表示，巨噬细胞被认为有助于慢性炎症的发生，如类风湿性关节炎。然而，在炎性关节病中巨噬细胞的起源和作用仍不清楚。

附：英文原文

Title: Locally renewing resident synovial macrophages provide a protective barrier for the joint

Author: Stephan Culemann, Anika Grneboom, Jos ngel Nicols-vila, Daniela Weidner, Katrin Franziska Lmmle, Tobias Rothe, Juan A. Quintana, Philipp Kirchner, Branislav Krljanac, Martin Eberhardt, Fulvia Ferrazzi, Elke Kretzschmar, Martin Schicht, Kim Fischer, Kolja Gelse, Maria Faas, Ren Pfeifle, Jochen A. Ackermann, Milena Pachowsky, Nina Renner, David Simon, Reiner F. Haseloff, Arif B. Ekici, Tobias Buerle, Ingolf E. Blasig, Julio Vera, David Voehringer, Arnd Kleyer, Friedrich Paulsen, Georg Schett, Andrs Hidalgo, Gerhard Kronke

Issue&Volume: Volume 572 Issue 7771

Abstract: Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1− mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.

DOI: 10.1038/s41586-019-1471-1

Source:https://www.nature.com/articles/s41586-019-1471-1