PPARγ Cistrome Repression during Activation of Lung Monocyte-Macrophages in Severe COVID-19

• Main Authors: Christophe Desterke, Ali G. Turhan, Annelise Bennaceur-Griscelli, Frank Griscelli
• Format: Article
• Language: English
• Published: Elsevier 2020-10-01
• Series: iScience
• Subjects: Immunology; Viral Microbiology; Transcriptomics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004220308038

Summary: 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.