IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2011

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

Nicolas Riteau
Gérard Eberl
Marc Le Bert
Bernhard Ryffel
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Résumé

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.
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Dates et versions

hal-00739655 , version 1 (08-10-2012)

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Paméla Gasse, Nicolas Riteau, Rachel Vacher, Marie-Laure Michel, Alain Fautrel, et al.. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.. PLoS ONE, 2011, 6 (8), pp.e23185. ⟨10.1371/journal.pone.0023185⟩. ⟨hal-00739655⟩
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