COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.

COVID - 19 和 RA 共有一个驱动 PD - L1 + 中性粒细胞和 CD14 + 单核细胞的 SPP1 髓样途径。

• 影响指数: 9.484
• 发表时间: 06 2021 18
• 来源期刊: JCI Insight
• DOI: 10.1172/jci.insight.147413
• PMID: 34143756
• 文章类型: Journal Article
• 作者列表: MacDonald L,Alivernini S,Tolusso B,Elmesmari A,Somma D,Perniola S,Paglionico A,Petricca L,Bosello SL,Carfì A,Sali M,Stigliano E,Cingolani A,Murri R,Arena V,Fantoni M,Antonelli M,Landi F,Franceschi F,Sanguinetti M,McInnes IB,McSharry C,Gasbarrini A,Otto TD,Kurowska-Stolarska M,Gremese E

关键词: Autoimmune diseases; Infectious disease; Inflammation; Macrophages

Mesh: Arthritis, Rheumatoid / immunology metabolism; B7-H1 Antigen / immunology; Bronchoalveolar Lavage Fluid / immunology; CD48 Antigen / immunology; COVID-19 / chemically induced immunology metabolism; Fatty Acid-Binding Proteins / immunology; Humans; Lectins / immunology; Lipopolysaccharide Receptors / immunology metabolism; Lung / diagnostic imaging immunology metabolism pathology; Macrophages / immunology metabolism; Membrane Glycoproteins / immunology; Monocytes / immunology metabolism; Neutrophils / immunology metabolism; Osteopontin / blood immunology; Receptor Protein-Tyrosine Kinases / metabolism; Receptors, Immunologic / immunology; S100A12 Protein / immunology metabolism; Synovial Membrane / immunology; Tomography, X-Ray Computed; Ficolins

Abstract

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.

摘要

我们探讨了慢性炎症性关节炎与COVID-19致病和巨噬细胞通路解析之间的潜在联系及其在COVID-19发病机制中的作用。我们发现重症COVID-19中主要的支气管肺泡灌洗液（BALF）巨噬细胞簇FCN1和FCN1SPP1与引起类风湿关节炎（RA）滑膜炎的滑膜组织巨噬细胞（STM）簇CD48hiS100A12和CD48SPP1转录相关。健康肺中占主导地位的BALF巨噬细胞簇FABP4+与控制RA缓解期滑膜炎消退的STM簇TREM2+转录相关。在严重的COVID-19中，SPP1和S100A12（与活动性RA共有的巨噬细胞簇的关键产物）的血浆浓度很高，并预测需要重症监护病房转移，他们在后COVID-19阶段仍然很高。与其他原因的重症肺炎相比，高血浆SPP1是重症COVID-19特有的，免疫组化在COVID-19肺肺泡中定位SPP1+巨噬细胞。对SPP1作用机制的研究表明，它驱动CD14+单核细胞的促炎激活和PD-L1+中性粒细胞的发展，严重COVID-19的两个标志。总之,COVID-19肺炎似乎是由与RA相似的致病性骨髓细胞途径驱动的，它们的介质如SPP1可能是严重COVID-19异常先天反应的上游激活剂，并预测包括COVID-19后病理在内的疾病轨迹。