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首页> 外文期刊>Nature >Locally renewing resident synovial macrophages provide a protective barrier for the joint
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Locally renewing resident synovial macrophages provide a protective barrier for the joint

机译：局部更新居民滑膜巨噬细胞为关节提供了一种保护屏障

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摘要

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.
机译：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，巨噬细胞在炎症关节疾病中的确切起源和作用都尚不清楚。在这里，我们使用命运映射方法与三维光板荧光显微镜和单细胞RNA测序结合，以对健康和发炎的关节内巨噬细胞亚组的组成，起源和分化进行综合时空分析，研究这些巨噬细胞在关节炎期间的角色。我们发现动态膜间结构，由CX（3）CR1（+）组织血液血栓药物的不同群体组成，在滑膜衬里形成内部免疫屏障，并物理地避开关节。这些障碍形成巨噬细胞显示出典型上皮细胞的特征，并通过嵌入滑膜组织的局部增殖Cx（3）Cr1（ - ）单核细胞库中保持它们的数量。与募集的单核细胞衍生的巨噬细胞不同，这激发了关节炎症，这些上皮样CX（3）Cr1（+）衬里巨噬细胞通过为关节内结构提供紧密结介导的屏蔽来限制炎症反应。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，对巨噬细胞在健康和疾病中的一般作用具有重要意义。

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  • 来源
    《Nature》 |2019年第7771期|670-675|共6页
  • 作者

    Culemann Stephan; Grueneboom Anika; Angel Nicolas-Avila Jose; Weidner Daniela; Laemmle Katrin Franziska; Rothe Tobias; Quintana Juan A.; Kirchner Philipp; Krljanac Branislav; Eberhardt Martin; Ferrazzi Fulvia; Kretzschmar Elke; Schicht Martin; Fischer Kim; Gelse Kolja; Faas Maria; Pfeifle Rene; Ackermann Jochen A.; Pachowsky Milena; Renner Nina; Simon David; Haseloff Reiner F.; Ekici Arif B.; Baeuerle Tobias; Blasig Ingolf E.; Vera Julio; Voehringer David; Kleyer Arnd; Paulsen Friedrich; Schett Georg; Hidalgo Andres; Kroenke Gerhard;

  • 作者单位

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Ctr Nacl Invest Cardiovasc Carlos III Area Cell & Dev Biol Madrid Spain;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Ctr Nacl Invest Cardiovasc Carlos III Area Cell & Dev Biol Madrid Spain;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Inst Human Genet Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Univ Klinikum Erlangen Dept Infect Biol Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Dept Dermatol Lab Syst Tumor Immunol Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Inst Human Genet Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Dept Funct & Clin Anat Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Dept Funct & Clin Anat Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Univ Klinikum Erlangen Dept Trauma Surg Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Univ Klinikum Erlangen Dept Trauma Surg Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Univ Klinikum Erlangen Dept Trauma Surg Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany;

    Leibniz Res Inst Mol Pharmacol Berlin Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Inst Human Genet Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen PIPE Inst Radiol Erlangen Germany;

    Leibniz Res Inst Mol Pharmacol Berlin Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Dept Dermatol Lab Syst Tumor Immunol Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Univ Klinikum Erlangen Dept Infect Biol Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany;

    Friedrich Alexander Univ Erlangen Nurnberg FAU Dept Funct & Clin Anat Erlangen Germany;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany;

    Ctr Nacl Invest Cardiovasc Carlos III Area Cell & Dev Biol Madrid Spain;

    Univ Klinikum Erlangen Dept Internal Med Rheumatol & Immunol 3 Erlangen Germany|Friedrich Alexander Univ Erlangen Nurnberg FAU Erlangen Germany|Univ Klinikum Erlangen Nikolaus Fiebiger Ctr Mol Med Erlangen Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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