Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19.
Cell Res
; 30(12): 1078-1087, 2020 12.
Article
in English
| MEDLINE | ID: covidwho-912896
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)-ß 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interferons
/
Receptors, Aryl Hydrocarbon
/
Mucus
Limits:
Animals
/
Humans
Language:
English
Journal:
Cell Res
Year:
2020
Document Type:
Article
Affiliation country:
S41422-020-00435-z
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