1. TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model.
- Author
-
Lee, Hyun Seung, Park, Heung-Woo, Song, Woo-Jung, Jeon, Eun Young, Bang, Boram, Shim, Eun-jin, Moon, Hyung-Geun, Kim, Yoon-Keun, Kang, Hye-Ryun, Min, Kyung-Up, and Cho, Sang-Heon
- Subjects
- *
IMMUNOREGULATION , *INTERLEUKIN-23 , *TH2 cells , *TUMOR necrosis factors , *ASTHMA , *LABORATORY rats , *AIRWAY (Anatomy) - Abstract
Background TNF-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. Objective To evaluate detailed mechanisms for the modulation of IL-23 by TNF-α in sensitization period. Methods During 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. Results Treatment 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. Conclusion TNF-α plays an important role in the development of airway inflammation by enhancing IL-23/Th17 and Th2 immune responses. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF