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

• TNF-α is important during sensitization period in low dose LPS/OA model.
• TNF-α enhances both Th2 and Th17 immune response regulating by IL-23.
• TNF-α upregulates the population of IL-23 secreting CD11c+ cells in sensitization.
• IL-23p19-secreting CD11c+ cells by TNF-α can induce Th2 and Th17 cells.

BackgroundTNF-α has been postulated to be a critical mediator contributing to airway inflammation. The purpose of this study was to evaluate the role of TNF-α in the induction of Th17 and Th2 cells related to asthma pathogenesis.ObjectiveTo evaluate detailed mechanisms for the modulation of IL-23 by TNF-α in sensitization period.MethodsDuring sensitization period, 10 μg of rat anti-mouse TNF-α mAb was intravenously administrated one hour before the application of OVA and 0.1 μg of LPS. To see the relation between TNF-α and associated effectors cytokine, we replenished TNF-α 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-α Ab.ResultsTreatment of anti-TNF-α mAb during sensitization period significantly reduced airway eosinophilia, serum OVA-specific IgE levels and methacholine AHR compared to isotype Ab. Anti-TNF-α 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-α KO mice resulted in complete restoration of eosinophilic airway inflammation, AHR, and IL-17A and IL-4 expression in CD4+ T cells. Anti-TNF-α mAb treatment after sensitization significantly diminished the population of IL-23p19-secreting CD11c+ cells in lung.ConclusionTNF-α plays an important role in the development of airway inflammation by enhancing IL-23/Th17 and Th2 immune responses.