PPARγ Cistrome Repression during Activation of Lung Monocyte-Macrophages in Severe COVID-19.
PPARγ Cistrome Repression during Activation of Lung Monocyte-Macrophages in Severe COVID-19.
复制标题
重症COVID-19患者肺单核巨噬细胞活化过程中PPARγ胞浆抑制
DOI：
10.1016/j.isci.2020.101611
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发表时间：
2020-10-23
期刊：
影响因子：
5.8
通讯作者：
Griscelli F
中科院分区：
文献类型：
--
作者：
Desterke C;Turhan AG;Bennaceur-Griscelli A;Griscelli F
严重COVID-19感染患者中细胞因子风暴的分子机制知之甚少。为了揭示这些事件，我们对COVID-19患者的肺活检组织进行了转录组分析，揭示了与PPARγ敲除巨噬细胞相似的基因富集模式。支气管肺泡灌洗液的单细胞基因表达分析揭示了CD 14 +/CD 16+细胞中PPARγ相关紊乱的特征性轨迹。我们确定了疾病严重程度与PPARγ复合物的几个成员（如EP 300、RXRA、RARA、SUMO 1、NR 3C 1和CCDC 88 A）表达减少的相关性。ChIP-seq分析证实了COVID-19肺样本中PPARγ-RXRA-NR 3C 1顺反组的抑制。对蛋白质-蛋白质网络的进一步分析强调了PPARγ相关蛋白SUMO 1与SARS病毒核蛋白之间的相互作用。总体而言，这些结果首次证明了PPARγ复合物参与严重的COVID-19肺病，并强烈表明其在主要单核细胞/巨噬细胞介导的炎症风暴中的作用。在严重COVID-19患者的炎症肺中，PPARγ表达受到抑制。在COVID-19患者的支气管肺泡CD 14 +/CD 16+细胞中，PPARγ轨迹被破坏。我们在此报告了在这种情况下，PPARγ-NR 3R 1-RXRA顺式组的表观遗传学抑制SUMO 1，作为受抑制的PPARγ伴侣，与人SARS病毒的核蛋白相互作用。免疫学;病毒微生物学;转录组学
The molecular mechanisms of cytokine storm in patients with severe COVID-19 infections are poorly understood. To uncover these events, we performed transcriptome analyses of lung biopsies from patients with COVID-19, revealing a gene enrichment pattern similar to that of PPARγ-knockout macrophages. Single-cell gene expression analysis of bronchoalveolar lavage fluids revealed a characteristic trajectory of PPARγ-related disturbance in the CD14+/CD16+ cells. We identified a correlation with the disease severity and the reduced expression of several members of the PPARγ complex such as EP300, RXRA, RARA, SUMO1, NR3C1, and CCDC88A. ChIP-seq analyses confirmed repression of the PPARγ-RXRA-NR3C1 cistrome in COVID-19 lung samples. Further analysis of protein-protein networks highlighted an interaction between the PPARγ-associated protein SUMO1 and a nucleoprotein of the SARS virus. Overall, these results demonstrate for the first time the involvement of the PPARγ complex in severe COVID-19 lung disease and suggest strongly its role in the major monocyte/macrophage-mediated inflammatory storm. PPARγ expression is repressed in inflammatory lungs of patients with severe COVID-19 PPARγ trajectory is disrupted in bronchoalveolar CD14+/CD16+ cells of patients with COVID-19 We report here the epigenetics repression of PPARγ-NR3R1-RXRA cistrome in this setting SUMO1, as repressed PPARγ partner, interacts with nucleoprotein of the human SARS virus Immunology; Viral Microbiology; Transcriptomics
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DOI：
10.4049/jimmunol.181.8.5646
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jennewein C;Kuhn AM;Schmidt MV;Meilladec-Jullig V;von Knethen A;Gonzalez FJ;Brüne B
通讯作者：
Brüne B
影响因子：
15.9
作者：
Bell-Parikh, LC;Ide, T;FitzGerald, GA
通讯作者：
FitzGerald, GA
影响因子：
15.9
作者：
Li, AC;Brown, KK;Glass, CK
通讯作者：
Glass, CK
影响因子：
7.3
作者：
Heming M;Gran S;Jauch SL;Fischer-Riepe L;Russo A;Klotz L;Hermann S;Schäfers M;Roth J;Barczyk-Kahlert K
通讯作者：
Barczyk-Kahlert K
影响因子：
3.7
作者：
Bournazos, Stylianos;Wang, Taia T.;Ravetch, Jeffrey V.
通讯作者：
Ravetch, Jeffrey V.