Locally renewing resident synovial macrophages provide a protective barrier for the joint
Locally renewing resident synovial macrophages provide a protective barrier for the joint
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DOI：
10.1038/s41586-019-1471-1
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发表时间：
2019-08-29
期刊：
影响因子：
64.8
通讯作者：
Kroenke, Gerhard
中科院分区：
文献类型：
--
作者：
Culemann, Stephan;Grueneboom, Anika;Kroenke, Gerhard
巨噬细胞被认为有助于慢性炎症性疾病，如类风湿性关节炎（1）。然而，巨噬细胞在炎症性关节疾病中的确切起源和作用仍不清楚。在这里，我们结合三维光片荧光显微镜和单细胞RNA测序使用命运映射方法，对健康和炎症关节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。我们发现，动态膜样结构，包括一个独特的群体CX（3）CR 1（+）组织驻留的巨噬细胞，形成一个内部的免疫屏障，在滑膜衬里和物理隔离的关节。这些屏障形成巨噬细胞显示上皮细胞的典型特征，并通过嵌入滑膜组织的局部增殖CX（3）CR 1（-）单核细胞池维持其数量。与活跃地促进关节炎症的单核细胞源性巨噬细胞不同，这些上皮样CX（3）CR 1（+）衬里巨噬细胞通过为关节内结构提供紧密连接介导的屏障来限制炎症反应。我们的数据揭示了滑膜巨噬细胞中意想不到的功能多样化，并对巨噬细胞在健康和疾病中的一般作用具有重要意义。
Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis(1). 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 membranelike structures, consisting of a distinct population of CX(3)CR1(+) 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 CX(3)CR1(-) mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX(3)CR1(+) lining macrophages restrict the inflammatory reaction by providing a tight-junctionmediated 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.