Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract.

Autor:	Smith JC; Google, Inc., New York City, NY 10011, USA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Sausville EL; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Girish V; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Stony Brook University, Stony Brook, NY 11794, USA., Yuan ML; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Johns Hopkins University, Baltimore, MD 21218, USA., Vasudevan A; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., John KM; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Hofstra University, Hempstead, NY 11549, USA., Sheltzer JM; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: sheltzer@cshl.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2020 Jun 08; Vol. 53 (5), pp. 514-529.e3. Date of Electronic Publication: 2020 May 16.
DOI:	10.1016/j.devcel.2020.05.012
Abstrakt:	The factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of secretory cells in the respiratory tract. Chronic smoke exposure triggers the expansion of this cell population and a concomitant increase in ACE2 expression. In contrast, quitting smoking decreases the abundance of these secretory cells and reduces ACE2 levels. Finally, we demonstrate that ACE2 expression is responsive to inflammatory signaling and can be upregulated by viral infections or interferon treatment. Taken together, these results may partially explain why smokers are particularly susceptible to severe SARS-CoV-2 infections. Furthermore, our work identifies ACE2 as an interferon-stimulated gene in lung cells, suggesting that SARS-CoV-2 infections could create positive feedback loops that increase ACE2 levels and facilitate viral dissemination. Competing Interests: Declaration of Interests J.C.S. is a co-founder of Meliora Therapeutics and is an employee of Google, Inc. This work was performed outside of her affiliation with Google and used no proprietary knowledge or materials from Google. J.M.S. has received consulting fees from Ono Pharmaceuticals, is a member of the Advisory Board of Tyra Biosciences, and is a co-founder of Meliora Therapeutics. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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