COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.
COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.
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新冠病毒病（COVID-19）与类风湿性关节炎（RA）共享一条分泌性磷蛋白1（SPP1）髓系通路，该通路可促使产生程序性死亡配体1阳性（PD-L1+）的中性粒细胞和CD14阳性（CD14+）的单核细胞。
DOI：
10.1172/jci.insight.147413
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发表时间：
2021-06-18
期刊：
影响因子：
8
通讯作者：
Gremese E
中科院分区：
文献类型：
--
作者：
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
我们探讨了慢性炎性关节炎与COVID-19致病性和溶解性巨噬细胞途径之间的潜在联系及其在COVID-19发病机制中的作用。我们发现，在严重的COVID-19中占主导地位的支气管肺泡灌洗液（BALF）巨噬细胞簇FCN1+和FCN1+SPP1+与滑膜组织巨噬细胞（STM）簇CD48hiS100A12+和CD48+SPP1+转录相关，这些细胞簇驱动类风湿性关节炎（RA）滑膜炎。在健康肺中占主导地位的BALF巨噬细胞簇FABP4+与类风湿关节炎缓解期滑膜炎消退的STM簇TREM2+转录相关。SPP1和S100A12（与活动性RA共享的巨噬细胞集群的关键产物）的血浆浓度在严重的COVID-19中较高，并预测需要转入重症监护病房，并且在COVID-19后阶段保持较高水平。与其他原因引起的重症肺炎相比，重症COVID-19患者血浆中SPP1水平较高，IHC定位了COVID-19肺肺泡中的SPP1+巨噬细胞。对SPP1作用机制的研究表明，它可以促进CD14+单核细胞的促炎激活和PD-L1+中性粒细胞的发育，这两者都是严重COVID-19的标志。总之，COVID-19肺炎似乎由与RA相似的致病性髓样细胞途径驱动，其介质如SPP1可能是严重COVID-19异常先天反应的上游激活因子，并预测疾病轨迹，包括COVID-19后病理。
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.
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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