Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice
Summary: Detecting cytoplasmic or extracellular DNA from host or pathogen origin by DNA sensor cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggers immune responses with secretion of type I interferons and inflammatory cytokines. However, STING agonists function as type...
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Elsevier
2025-05-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225005851 |
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| author | Pauline Chenuet Manon Mellier Yasmine Messaoud-Nacer Elodie Culerier Quentin Marquant Louis Fauconnier Nathalie Rouxel Aurélie Ledru Stéphanie Rose Bernhard Ryffel Lionel Apetoh Valérie F.J. Quesniaux Dieudonnée Togbe |
| author_facet | Pauline Chenuet Manon Mellier Yasmine Messaoud-Nacer Elodie Culerier Quentin Marquant Louis Fauconnier Nathalie Rouxel Aurélie Ledru Stéphanie Rose Bernhard Ryffel Lionel Apetoh Valérie F.J. Quesniaux Dieudonnée Togbe |
| author_sort | Pauline Chenuet |
| collection | DOAJ |
| description | Summary: Detecting cytoplasmic or extracellular DNA from host or pathogen origin by DNA sensor cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggers immune responses with secretion of type I interferons and inflammatory cytokines. However, STING agonists function as type-2 adjuvant promoting allergic asthma. Here, we asked how cGAS/STING signaling pathway influences allergen-induced type-2 immune responses in models of allergic airway diseases induced by birch pollen extract, house dust mite, or ovalbumin plus Alum. We report increased extracellular dsDNA in the airways, together with cGAS and STING gene expression, following allergen challenge in these models, correlating dsDNA and type-2 cytokine IL-4, IL-5, and IL-13 release. Allergen-induced type-2 immune responses were reduced in cGAS- or STING-deficient mice. Further, blocking cGAS function with the specific inhibitor RU.521 protected mice from birch pollen allergen-induced airway inflammation and type-2 immune responses. Thus, DNA sensing by cGAS contributes to type-2 immune responses and may represent a therapeutic target for allergic lung inflammation. |
| format | Article |
| id | doaj-art-e6849f383a704ea0a192b914ccfd2f89 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-e6849f383a704ea0a192b914ccfd2f892025-08-20T03:09:03ZengElsevieriScience2589-00422025-05-0128511232410.1016/j.isci.2025.112324Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in micePauline Chenuet0Manon Mellier1Yasmine Messaoud-Nacer2Elodie Culerier3Quentin Marquant4Louis Fauconnier5Nathalie Rouxel6Aurélie Ledru7Stéphanie Rose8Bernhard Ryffel9Lionel Apetoh10Valérie F.J. Quesniaux11Dieudonnée Togbe12Artimmune SAS, 13 Avenue Buffon, 45100 Orléans, FranceArtimmune SAS, 13 Avenue Buffon, 45100 Orléans, FranceLaboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, FranceLaboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, FranceLaboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, FranceArtimmune SAS, 13 Avenue Buffon, 45100 Orléans, FranceArtimmune SAS, 13 Avenue Buffon, 45100 Orléans, FranceArtimmune SAS, 13 Avenue Buffon, 45100 Orléans, FranceLaboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, FranceArtimmune SAS, 13 Avenue Buffon, 45100 Orléans, France; Laboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, FranceBrown Center for Immunotherapy, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USALaboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, France; Corresponding authorLaboratory of Immuno-Neuro Modulation (INEM), UMR 7355 CNRS and University of Orleans, 3B rue de la Ferollerie, 45071 Orleans-Cedex, France; University of Orleans, 45000 Orleans, France; Corresponding authorSummary: Detecting cytoplasmic or extracellular DNA from host or pathogen origin by DNA sensor cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggers immune responses with secretion of type I interferons and inflammatory cytokines. However, STING agonists function as type-2 adjuvant promoting allergic asthma. Here, we asked how cGAS/STING signaling pathway influences allergen-induced type-2 immune responses in models of allergic airway diseases induced by birch pollen extract, house dust mite, or ovalbumin plus Alum. We report increased extracellular dsDNA in the airways, together with cGAS and STING gene expression, following allergen challenge in these models, correlating dsDNA and type-2 cytokine IL-4, IL-5, and IL-13 release. Allergen-induced type-2 immune responses were reduced in cGAS- or STING-deficient mice. Further, blocking cGAS function with the specific inhibitor RU.521 protected mice from birch pollen allergen-induced airway inflammation and type-2 immune responses. Thus, DNA sensing by cGAS contributes to type-2 immune responses and may represent a therapeutic target for allergic lung inflammation.http://www.sciencedirect.com/science/article/pii/S2589004225005851Immune responseImmunologyMolecular biology |
| spellingShingle | Pauline Chenuet Manon Mellier Yasmine Messaoud-Nacer Elodie Culerier Quentin Marquant Louis Fauconnier Nathalie Rouxel Aurélie Ledru Stéphanie Rose Bernhard Ryffel Lionel Apetoh Valérie F.J. Quesniaux Dieudonnée Togbe Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice iScience Immune response Immunology Molecular biology |
| title | Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice |
| title_full | Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice |
| title_fullStr | Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice |
| title_full_unstemmed | Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice |
| title_short | Birch pollen allergen-induced dsDNA release activates cGAS-STING signaling and type 2 immune response in mice |
| title_sort | birch pollen allergen induced dsdna release activates cgas sting signaling and type 2 immune response in mice |
| topic | Immune response Immunology Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225005851 |
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