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

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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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
Medicine
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Science
Q
Acceso en línea:https://doaj.org/article/1b64d5b4f1e24497ad66eea3c45ab271
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Sumario:<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.

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