T helper (Th)17 immune response participates in allergic lung inflammation and asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL-17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia, cytokine and chemokine production as found in absence of IL-17RA. Furthermore, specific antibody neutralization of either IL-17A or IL-17F given during the sensitization phase attenuated allergic lung inflammation and airway hyperreactivity. In vitro activation by HDM of primary dendritic cells revealed a comparable induction of CXCL1 and IL-6 expression and the response to IL-17A and IL-17F relied on IL-17RA signaling via the adaptor protein act1 in fibroblasts. Therefore, HDM-induced allergic respiratory response depends on IL-17RA via act1 signaling and inactivation of either IL-17A or IL-17F is sufficient to attenuate allergic asthma in mice.
Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice
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Pauline Chenuet, Louis Fauconnier, Fahima Madouri, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Pascal Mauny, Rachel Lory, Catherine Uttenhove, Jacques van Snick, Yoichiro Iwakura, Franco di Padova, Valérie Quesniaux, Dieudonnée Togbe, Bernhard Ryffel; Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice. Clin Sci (Lond) 1 October 2017; 131 (20): 2533–2548. doi: https://doi.org/10.1042/CS20171034
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