PT  - JOURNAL ARTICLE
AU  - Rongchang Chen
AU  - Qinglin Zhang
AU  - Shuyu Chen
AU  - Haixiong Tang
AU  - Peikai Huang
AU  - Shushan Wei
AU  - Lihong Yao
TI  - IL-17F, rather than IL-17A, underlies airway inflammation in a steroid insensitive toluene diisocyanate-induced asthma model
AID  - 10.1183/13993003.01510-2018
DP  - 2019 Jan 01
TA  - European Respiratory Journal
PG  - 1801510
4099  - http://erj.ersjournals.com/content/early/2019/01/10/13993003.01510-2018.short
4100  - http://erj.ersjournals.com/content/early/2019/01/10/13993003.01510-2018.full
AB  - Steroid insensitivity constitutes the major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both Th2 and Th17 responses and is often associated with poor responsiveness to steroid treatment in the clinic. We sought to evaluate the effects of inhaled and systemic steroids on a TDI-induced asthma model and to find how IL-17A and IL-17F function in this model. BALB/c mice were exposed to TDI for generating an asthma model, and were treated with inhaled fluticasone propionate (FP), systemic prednisone (Pred), anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL17F. Both FP and Pred showed no effects on TDI-induced airway hyperreactivity (AHR), bronchial neutrophilia and eosinophilia, epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by FP or Pred. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses. While anti-IL-17F ameliorated TDI-induced AHR and airway neutrophilia, with decreased Th17 responses. Recombinant IL-17A and IL-17F showed opposite effects to the monoclonal antibodies. In conclusion, IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is irresponsive to both inhaled and systemic steroids.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Chen has nothing to disclose.Conflict of interest: Dr. Chen has nothing to disclose.Conflict of interest: Dr. Huang has nothing to disclose.Conflict of interest: Dr. Tang has nothing to disclose.Conflict of interest: Dr. Wei has nothing to disclose.Conflict of interest: Dr. Yao has nothing to disclose.Conflict of interest: Dr. Zhang has nothing to disclose.