Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice

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Nascimento, Mégane | Gombault, Aurélie | Lacerda-Queiroz, Norinne | Panek, Corinne | Savigny, Florence | Sbeity, Malak | Bourinet, Manon | Le Bert, Marc | Riteau, Nicolas | Ryffel, Bernhard | Quesniaux, Valérie | Couillin, Isabelle

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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