TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model. (March 2016)

• Record Type: Journal Article
• Authors: 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; Cho, Sang-Heon
• Is Part Of: Cytokine. Volume 79(2016)
• Page Start: 23
• Page End: 30
• Publication Date: 2016-03
• Subjects: TNF-α -- IL-23 -- Th17; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.12.001
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: 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. 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.