tetano
Editor, Senior Moderator
Cell Res
. 2020 Nov 6.
doi: 10.1038/s41422-020-00435-z. Online ahead of print.
Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19
Yuying Liu[SUP] 1 2 [/SUP], Jiadi Lv[SUP] 1 [/SUP], Jiangning Liu[SUP] 3 [/SUP], Man Li[SUP] 4 [/SUP], Jing Xie[SUP] 1 [/SUP], Qi Lv[SUP] 3 [/SUP], Wei Deng[SUP] 3 [/SUP], Nannan Zhou[SUP] 1 [/SUP], Yabo Zhou[SUP] 1 [/SUP], Jiangping Song[SUP] 5 [/SUP], Peng Wang[SUP] 4 [/SUP], Chuan Qin[SUP] 3 [/SUP], Wei-Min Tong[SUP] 6 [/SUP], Bo Huang[SUP] 7 8 9 [/SUP]
Affiliations
Abstract
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.
. 2020 Nov 6.
doi: 10.1038/s41422-020-00435-z. Online ahead of print.
Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19
Yuying Liu[SUP] 1 2 [/SUP], Jiadi Lv[SUP] 1 [/SUP], Jiangning Liu[SUP] 3 [/SUP], Man Li[SUP] 4 [/SUP], Jing Xie[SUP] 1 [/SUP], Qi Lv[SUP] 3 [/SUP], Wei Deng[SUP] 3 [/SUP], Nannan Zhou[SUP] 1 [/SUP], Yabo Zhou[SUP] 1 [/SUP], Jiangping Song[SUP] 5 [/SUP], Peng Wang[SUP] 4 [/SUP], Chuan Qin[SUP] 3 [/SUP], Wei-Min Tong[SUP] 6 [/SUP], Bo Huang[SUP] 7 8 9 [/SUP]
Affiliations
- PMID: 33159154
- DOI: 10.1038/s41422-020-00435-z
Abstract
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.