1. Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis
- Author
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Mégane Nascimento, Sarah Huot-Marchand, Corinne Schricke, F. Savigny, Marc Le Bert, Aurélie Gombault, Isabelle Couillin, Felipe Da Gama Monteiro, Norinne Lacerda-Queiroz, Mélanie Meda, Nicolas Riteau, and Bernhard Ryffel
- Subjects
lcsh:Immunologic diseases. Allergy ,Male ,mice ,Immunology ,Receptor, Interferon alpha-beta ,IL-28 ,Bleomycin ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Interferon ,Nucleic Acids ,Pulmonary fibrosis ,medicine ,Animals ,Immunology and Allergy ,Lung ,Original Research ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,business.industry ,Interstitial lung disease ,Membrane Proteins ,respiratory system ,idiopathic pulmonary fibrosis ,self-DNA recognition ,medicine.disease ,Nucleotidyltransferases ,eye diseases ,respiratory tract diseases ,3. Good health ,Mice, Inbred C57BL ,Disease Models, Animal ,Sting ,030220 oncology & carcinogenesis ,Stimulator of interferon genes ,Nucleic acid ,Collagen ,lcsh:RC581-607 ,business ,Bronchoalveolar Lavage Fluid ,Intracellular ,STING ,medicine.drug - Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of interstitial lung disease for which current treatments display limited efficacy. IPF is largely driven by host-derived danger signals released upon recurrent local tissue damage. Here we explored the roles of self-DNA and stimulator of interferon genes (STING), a protein belonging to an intracellular DNA sensing pathway that leads to type I and/or type III interferon (IFN) production upon activation. Using a mouse model of IPF, we report that STING deficiency leads to exacerbated pulmonary fibrosis with increased collagen deposition in the lungs and excessive remodeling factors expression. We further show that STING-mediated protection does not rely on type I IFN signaling nor on IL-17A or TGF-β modulation but is associated with dysregulated neutrophils. Together, our data support an unprecedented immunoregulatory function of STING in lung fibrosis.
- Published
- 2021
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