1. Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice
- Author
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Mégane Nascimento, Aurélie Gombault, Norinne Lacerda-Queiroz, Corinne Panek, Florence Savigny, Malak Sbeity, Manon Bourinet, Marc Le Bert, Nicolas Riteau, Bernhard Ryffel, Valérie F. J. Quesniaux, and Isabelle Couillin
- Subjects
Medicine ,Science - Abstract
Abstract Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.
- Published
- 2019
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