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</...
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2011
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oai:doaj.org-article:1b64d5b4f1e24497ad66eea3c45ab2712021-11-18T06:47:54ZIL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.1932-620310.1371/journal.pone.0023185https://doaj.org/article/1b64d5b4f1e24497ad66eea3c45ab2712011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858022/?tool=EBIhttps://doaj.org/toc/1932-6203<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.Paméla GasseNicolas RiteauRachel VacherMarie-Laure MichelAlain FautrelFranco di PadovaLizette FickSabine CharronVincent LagenteGérard EberlMarc Le BertValérie F J QuesniauxFrançois HuauxMaria Leite-de-MoraesBernhard RyffelIsabelle CouillinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23185 (2011) |
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DOAJ |
| language |
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| topic |
Medicine R Science Q |
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Medicine R Science Q 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. |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
il-1 and il-23 mediate early il-17a production in pulmonary inflammation leading to late fibrosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/1b64d5b4f1e24497ad66eea3c45ab271 |
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