Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice

2017 ◽  
Vol 131 (20) ◽  
pp. 2533-2548 ◽  
Author(s):  
Pauline Chenuet ◽  
Louis Fauconnier ◽  
Fahima Madouri ◽  
Tiffany Marchiol ◽  
Nathalie Rouxel ◽  
...  

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.

2015 ◽  
Vol 309 (8) ◽  
pp. L768-L775 ◽  
Author(s):  
Johannes D. de Boer ◽  
Lea C. Berkhout ◽  
Sacha F. de Stoppelaar ◽  
Jack Yang ◽  
Roelof Ottenhoff ◽  
...  

Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology ( P < 0.05) and decreased IL-4 levels ( P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.


2015 ◽  
Vol 45 (4) ◽  
pp. 1116-1128 ◽  
Author(s):  
Katie E. Burrows ◽  
Celine Dumont ◽  
Clare L. Thompson ◽  
Matthew C. Catley ◽  
Kate L. Dixon ◽  
...  

2013 ◽  
Vol 20 (6) ◽  
pp. 618-625 ◽  
Author(s):  
J Daan de Boer ◽  
Cornelis van’t Veer ◽  
Ingrid Stroo ◽  
Anne J van der Meer ◽  
Alex F de Vos ◽  
...  

2015 ◽  
Vol 7 (4) ◽  
pp. 351-365 ◽  
Author(s):  
Fahima Madouri ◽  
Noëlline Guillou ◽  
Louis Fauconnier ◽  
Tiffany Marchiol ◽  
Nathalie Rouxel ◽  
...  

Allergy ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 1217-1228 ◽  
Author(s):  
Evgeniia Korotchenko ◽  
Raquel Moya ◽  
Sandra Scheiblhofer ◽  
Isabella A Joubert ◽  
Jutta Horejs‐Hoeck ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Anne-Perrine Foray ◽  
Céline Dietrich ◽  
Coralie Pecquet ◽  
François Machavoine ◽  
Lucienne Chatenoud ◽  
...  

Allergic asthma is characterized by airway inflammation with a Th2-type cytokine profile, hyper-IgE production, mucus hypersecretion, and airway hyperreactivity (AHR). It is increasingly recognized that asthma is a heterogeneous disease implicating complex immune mechanisms resulting in distinct endotypes observed in patients. In this study, we showed that non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, undergo more severe allergic asthma airway inflammation and AHR than pro-Th2 BALB/c mice upon house dust mite (HDM) sensitization and challenge. The use of IL-4-deficient NOD mice and the in vivo neutralization of IL-17 demonstrated that both IL-4 and IL-17 are responsible by the exacerbated airway inflammation and AHR observed in NOD mice. Overall, our findings indicate that autoimmune diabetes-prone NOD mice might become useful as a new HDM-induced asthma model to elucidate allergic dysimmune mechanisms involving Th2 and Th17 responses that could better mimic some asthmatic endoytpes.


2018 ◽  
Vol 116 ◽  
pp. 32-41 ◽  
Author(s):  
Azam F. Tayabali ◽  
Yan Zhang ◽  
Jason H. Fine ◽  
Don Caldwell ◽  
Martha Navarro

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