PT  - JOURNAL ARTICLE
AU  - Rongchang Chen
AU  - Qingling Zhang
AU  - Shuyu Chen
AU  - Haixiong Tang
AU  - Peikai Huang
AU  - Shushan Wei
AU  - Zhenyu Liang
AU  - Xin Chen
AU  - Ailin Tao
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 Apr 01
TA  - European Respiratory Journal
PG  - 1801510
VI  - 53
IP  - 4
4099  - http://erj.ersjournals.com/content/53/4/1801510.short
4100  - http://erj.ersjournals.com/content/53/4/1801510.full
SO  - Eur Respir J2019 Apr 01; 53
AB  - Steroid insensitivity constitutes a major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both T-helper 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 interleukin (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, systemic prednisone, anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL-17F.Both fluticasone propionate and prednisone showed no effects on TDI-induced airway hyperresponsiveness (AHR), bronchial neutrophilia and eosinophilia, and epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by fluticasone propionate or prednisone. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses, whereas 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.IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is unresponsive to both inhaled and systemic steroids.In a TDI-induced steroid-insensitive murine asthma model, IL-17A restricts allergic responses through suppressing Th2 inflammation and eosinophil recruitment, while IL-17F modulates airway inflammation by driving Th17 response and neutrophil infiltrates http://ow.ly/vP2z30nk7Z3