IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.
<h4>Background</h4>Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice.<h4>Methods</...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858022/?tool=EBI |
| _version_ | 1797937945314852864 |
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| author | Paméla Gasse Nicolas Riteau Rachel Vacher Marie-Laure Michel Alain Fautrel Franco di Padova Lizette Fick Sabine Charron Vincent Lagente Gérard Eberl Marc Le Bert Valérie F J Quesniaux François Huaux Maria Leite-de-Moraes Bernhard Ryffel Isabelle Couillin |
| author_facet | Paméla Gasse Nicolas Riteau Rachel Vacher Marie-Laure Michel Alain Fautrel Franco di Padova Lizette Fick Sabine Charron Vincent Lagente Gérard Eberl Marc Le Bert Valérie F J Quesniaux François Huaux Maria Leite-de-Moraes Bernhard Ryffel Isabelle Couillin |
| author_sort | Paméla Gasse |
| collection | DOAJ |
| description | <h4>Background</h4>Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice.<h4>Methods</h4>The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice.<h4>Results</h4>We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis.<h4>Conclusions</h4>Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology. |
| first_indexed | 2024-04-10T18:52:10Z |
| format | Article |
| id | doaj.art-1b64d5b4f1e24497ad66eea3c45ab271 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T18:52:10Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1b64d5b4f1e24497ad66eea3c45ab2712023-02-01T05:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2318510.1371/journal.pone.0023185IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.Paméla GasseNicolas RiteauRachel VacherMarie-Laure MichelAlain FautrelFranco di PadovaLizette FickSabine CharronVincent LagenteGérard EberlMarc Le BertValérie F J QuesniauxFrançois HuauxMaria Leite-de-MoraesBernhard RyffelIsabelle Couillin<h4>Background</h4>Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice.<h4>Methods</h4>The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice.<h4>Results</h4>We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis.<h4>Conclusions</h4>Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858022/?tool=EBI |
| spellingShingle | Paméla Gasse Nicolas Riteau Rachel Vacher Marie-Laure Michel Alain Fautrel Franco di Padova Lizette Fick Sabine Charron Vincent Lagente Gérard Eberl Marc Le Bert Valérie F J Quesniaux François Huaux Maria Leite-de-Moraes Bernhard Ryffel Isabelle Couillin IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. PLoS ONE |
| title | IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. |
| title_full | IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. |
| title_fullStr | IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. |
| title_full_unstemmed | IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. |
| title_short | IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. |
| title_sort | il 1 and il 23 mediate early il 17a production in pulmonary inflammation leading to late fibrosis |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858022/?tool=EBI |
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