TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model

Background: TNF-alpha has been postulated to be a critical mediator contributing to airway inflammation. The purpose of this study was to evaluate the role of TNF-alpha in the induction of Th17 and Th2 cells related to asthma pathogenesis. Objective: To evaluate detailed mechanisms for the modulation of IL-23 by TNF-alpha in sensitization period. Methods: During sensitization period, 10 mu g of rat anti-mouse TNF-alpha mAb was intravenously administrated one hour before the application of OVA and 0.1 mu g of LPS. To see the relation between TNF-alpha and associated effectors cytokine, we replenished TNF-alpha KO mice with IL-23 during sensitization period. To assess cellular resources, CD11c+ cells isolated from lung tissue after sensitization were treated with anti-TNF-alpha Ab. Results: Treatment of anti-TNF-alpha mAb during sensitization period significantly reduced airway eosinophilia, serum OVA-specific IgE levels and methacholine AHR compared to isotype Ab. Anti-TNF-alpha mAb treated mice showed significant reduction in the levels of IL-23 after sensitization in bronchoalveolar lavage fluid (BALF) as well as IL-17A, IL-4 levels in BALF after challenge compared with isotype Ab treated mice. Supplementation of IL-23 in TNF-alpha KO mice resulted in complete restoration of eosinophilic airway inflammation, AHR, and IL-17A and IL-4 expression in CD4+ T cells. Anti-TNF-alpha mAb treatment after sensitization significantly diminished the population of IL-23p19-secreting CD11c+ cells in lung. Conclusion: TNF-alpha plays an important role in the development of airway inflammation by enhancing IL-23/Th17 and Th2 immune responses. (C) 2016 Published by Elsevier Ltd.