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

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

doi:10.1038/s41598-019-51427-y

Cited by 45 publications

(55 citation statements)

References 51 publications

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“…42 Additionally, acute exposure to cigarette smoke also causes airway inflammation with fibrosis and emphysema of mice in a STING-dependent manner. 43 Our recent study proposed that STING may drive NLRP3 inflammasome-mediated pyroptosis and cellular injury in sepsis-induced cardiac injury. 20 During liver ischemia and reperfusion, STING suppression of macrophages inhibited the overactivation of NLRP3 inflammasome and excessive secretion of IL-1β and IL-18, eventually reducing liver injury.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

Wang

Jiang

et al. 2020

Clinical & Translational Med

161

125

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Section: Discussionmentioning

confidence: 99%

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

Wang

Jiang

et al. 2020

Clinical & Translational Med

161

125

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“…This self-DNA activates the cGAS-STING pathway, triggering type I IFN-dependent lung inflammation, which is attenuated in cGAS, STING or type I IFN receptor-deficient mice. 120 Further investigation of whether the cGAS-STING pathway is also involved in self-DNA sensing and pathogenesis in COPD patients may lead to therapeutic targets.…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

“…100 In addition, cGAS-STING activation by self-DNA release upon cigarette smoke exposure leads to type I interferon-dependent lung inflammation. 120 Recently, Han et al reported that airway epithelial cGAS is critical for the induction of allergic airway inflammation in mice. 134 Altogether, these findings indicate cGAS-STING activation is a critical driver of lung inflammation.…”

Section: Lung Inflammation and Fibrosismentioning

confidence: 99%

The cGAS‐STING pathway: The role of self‐DNA sensing in inflammatory lung disease

Serrano

Davis

et al. 2020

FASEB j.

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The presence of DNA in the cytosol is usually a sign of microbial infections, which alerts the host innate immune system to mount a defense response. Cyclic GMP‐AMP synthase (cGAS) is a critical cytosolic DNA sensor that elicits robust innate immune responses through the production of the second messenger, cyclic GMP‐AMP (cGAMP), which binds and activates stimulator of interferon genes (STING). However, cGAS binds to DNA irrespective of DNA sequence, therefore, self‐DNA leaked from the nucleus or mitochondria can also serve as a cGAS ligand to activate this pathway and trigger extensive inflammatory responses. Dysregulation of the cGAS‐STING pathway is responsible for a broad array of inflammatory and autoimmune diseases. Recently, evidence has shown that self‐DNA release and cGAS‐STING pathway over‐activation can drive lung disease, making this pathway a promising therapeutic target for inflammatory lung disease. Here, we review recent advances on the cGAS‐STING pathway governing self‐DNA sensing, highlighting its role in pulmonary disease.

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“…Cigarette smoke is well described as injurious to pulmonary barrier function primarily due to epithelial cell injury and concurrent release of self-DNA and activation of the cGAS/STING pathway. 131 Downstream interferon signaling and neutrophilic infiltrates then contribute to tobacco smoke-related fibrosis and emphysematous changes, with IFNAR1-antibody acting to inhibit phenotypes in exposed mice. Complicating the story, another group has uncovered that STING is actually decreased in settings of cigarette-exposure-mediated DNA damage and release, resulting in worsened emphysema, though—again—a compensatory effect cannot be ruled out.…”

Section: Exposures and Therapymentioning

confidence: 99%

The Third Man: DNA sensing as espionage in pulmonary vascular health and disease

et al. 2021

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For as long as nucleic acids have been utilized to vertically and horizontally transfer genetic ma-terial, living organisms have had to develop methods of recognizing cytosolic DNA as either pathogenic (microbial invasion) or physiologic (mitosis and cellular proliferation). Derangement in key signaling molecules involved in these pathways of nucleotide sensing result in a family of diseases labeled interferonopathies. An interferonopathy, characterized by constitutive expres-sion of type I interferons, ultimately manifests as severe autoimmune disease at a young age. Afflicted patients present with a constellation of immune-mediated conditions, including primary lung manifestations such as pulmonary fibrosis and pulmonary hypertension. The latter condi-tion is especially interesting in light of the known role that DNA damage plays in a variety of types of inherited and induced pulmonary hypertension, with free DNA detection elevated in the circula-tion of affected individuals. While little is known regarding the role of cytosolic DNA sensing in development of pulmonary vascular disease, exciting new research in the related fields of immu-nology and oncology potentially sheds light on future areas of fruitful exploration. As such, the goal of this review is to summarize the state of the field of nucleic acid sensing, extrapolating common shared pathways that parallel our knowledge of pulmonary hypertension, in a molecular and cell-specific manner. Principles of DNA sensing related to known pulmonary injury inducing stimuli are also evaluated, in addition to potential therapeutic targets. Finally, future directions in pulmonary hypertension research and treatments will be briefly discussed.

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

Cited by 45 publications

References 51 publications

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

The cGAS‐STING pathway: The role of self‐DNA sensing in inflammatory lung disease

The Third Man: DNA sensing as espionage in pulmonary vascular health and disease

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