IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis

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dc.contributor.authorGasse, Pamélaen_ZA
dc.contributor.authorRiteau, Nicolasen_ZA
dc.contributor.authorVacher, Rachelen_ZA
dc.contributor.authorMichel, Marie-Laureen_ZA
dc.contributor.authorFautrel, Alainen_ZA
dc.contributor.authordi Padova, Francoen_ZA
dc.contributor.authorFick, Lizetteen_ZA
dc.contributor.authorCharron, Sabineen_ZA
dc.contributor.authorLagente, Vincenten_ZA
dc.contributor.authorEberl, Gérarden_ZA
dc.date.accessioned2016-01-02T05:05:49Z
dc.date.available2016-01-02T05:05:49Z
dc.date.issued2011en_ZA
dc.description.abstractBACKGROUND: 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. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: 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. CONCLUSIONS: 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.en_ZA
dc.identifier.apacitationGasse, P., Riteau, N., Vacher, R., Michel, M., Fautrel, A., di Padova, F., ... Eberl, G. (2011). IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. <i>PLoS One</i>, http://hdl.handle.net/11427/16164en_ZA
dc.identifier.chicagocitationGasse, Paméla, Nicolas Riteau, Rachel Vacher, Marie-Laure Michel, Alain Fautrel, Franco di Padova, Lizette Fick, Sabine Charron, Vincent Lagente, and Gérard Eberl "IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16164en_ZA
dc.identifier.citationGasse, P., Riteau, N., Vacher, R., Michel, M. L., Fautrel, A., Di Padova, F., ... & Le Bert, M. (2011). IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. PloS one, 6(8), e23185. doi:10.1371/journal.pone.0023185en_ZA
dc.identifier.ris TY - Journal Article AU - Gasse, Paméla AU - Riteau, Nicolas AU - Vacher, Rachel AU - Michel, Marie-Laure AU - Fautrel, Alain AU - di Padova, Franco AU - Fick, Lizette AU - Charron, Sabine AU - Lagente, Vincent AU - Eberl, Gérard AB - BACKGROUND: 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. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: 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. CONCLUSIONS: 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. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0023185 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis TI - IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis UR - http://hdl.handle.net/11427/16164 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16164
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0023185
dc.identifier.vancouvercitationGasse P, Riteau N, Vacher R, Michel M, Fautrel A, di Padova F, et al. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. PLoS One. 2011; http://hdl.handle.net/11427/16164.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Gasse et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherFibrosisen_ZA
dc.subject.otherCollagensen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherNeutrophilsen_ZA
dc.subject.otherPulmonary fibrosisen_ZA
dc.subject.otherInflammatory diseasesen_ZA
dc.titleIL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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