Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis
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 stim...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.588799/full |
| _version_ | 1818945002255941632 |
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| author | Florence Savigny Corinne Schricke Norinne Lacerda-Queiroz Mélanie Meda Mégane Nascimento Sarah Huot-Marchand Felipe Da Gama Monteiro Bernhard Ryffel Aurélie Gombault Marc Le Bert Isabelle Couillin Nicolas Riteau |
| author_facet | Florence Savigny Corinne Schricke Norinne Lacerda-Queiroz Mélanie Meda Mégane Nascimento Sarah Huot-Marchand Felipe Da Gama Monteiro Bernhard Ryffel Aurélie Gombault Marc Le Bert Isabelle Couillin Nicolas Riteau |
| author_sort | Florence Savigny |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T07:52:11Z |
| format | Article |
| id | doaj.art-389163174a7f427fb322494692ab58d4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T07:52:11Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-389163174a7f427fb322494692ab58d42022-12-21T19:47:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.588799588799Protective Role of the Nucleic Acid Sensor STING in Pulmonary FibrosisFlorence SavignyCorinne SchrickeNorinne Lacerda-QueirozMélanie MedaMégane NascimentoSarah Huot-MarchandFelipe Da Gama MonteiroBernhard RyffelAurélie GombaultMarc Le BertIsabelle CouillinNicolas RiteauIdiopathic 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.588799/fullidiopathic pulmonary fibrosisSTINGself-DNA recognitionmiceIL-28 |
| spellingShingle | Florence Savigny Corinne Schricke Norinne Lacerda-Queiroz Mélanie Meda Mégane Nascimento Sarah Huot-Marchand Felipe Da Gama Monteiro Bernhard Ryffel Aurélie Gombault Marc Le Bert Isabelle Couillin Nicolas Riteau Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis Frontiers in Immunology idiopathic pulmonary fibrosis STING self-DNA recognition mice IL-28 |
| title | Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis |
| title_full | Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis |
| title_fullStr | Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis |
| title_full_unstemmed | Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis |
| title_short | Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis |
| title_sort | protective role of the nucleic acid sensor sting in pulmonary fibrosis |
| topic | idiopathic pulmonary fibrosis STING self-DNA recognition mice IL-28 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.588799/full |
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