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Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19

2020; Springer Nature; Volume: 30; Issue: 12 Linguagem: Inglês

10.1038/s41422-020-00435-z

1748-7838

Yuying Liu, Jiadi Lv, Jiangning Liu, Man Li, Jing Xie, Qi Lv, Wei Deng, Nannan Zhou, Yabo Zhou, Jiangping Song, Peng Wang, Chuan Qin, Wei‐Min Tong, Bo Huang,

Respiratory viral infections research

Silent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-β or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.