title: TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model.
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, 10μg of rat anti-mouse TNF-α mAb was intravenously administrated one hour before the application of OVA and 0.1μg 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.
  
  
  CONCLUSIONS
  TNF-α plays an important role in the development of airway inflammation by enhancing IL-23/Th17 and Th2 immune responses.
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo-Jung
authors.initials: WJ
authors.lastname: Song
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Jeon
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Bang
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Shim
authors.affiliation: Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Hyung-Geun
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: shcho@snu.ac.kr.
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D020381:Interleukin-17 / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D039521:CD11c Antigen; C098680:Il17a protein, mouse; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: IL-23; TNF-α; Th17