title: An important role of tumor necrosis factor receptor-2 on natural killer T cells on the development of dsRNA-enhanced Th2 cell response to inhaled allergens.
abstract: BACKGROUND
  Recent evidence indicates that TNF-α is a key mediator of the development of dsRNA-enhanced Th2 cell response to inhaled allergens. Natural killer T (NKT) cells may be a candidate source of Th2-polarizing cytokines.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the role of lung NKT cells on the development of TNF-α-mediated Th2 cell response.
  
  
  METHODS
  A virus-associated asthma mouse model was generated by the administration of ovalbumin (OVA, 75 μg) and poly[I:C] (0.1 μg). Role of NKT and type I NKT cells was evaluated using CD1d- and Jα18-deficient mice. TNF-α receptors (TNFRs) were antagonized by using TNFR blocking peptides.
  
  
  RESULTS
  The number of infiltrated NKT cells was increased in a virus-associated asthma mouse model. Increase in Th2 and Th17 cytokine levels in wild-type mice were abolished in both CD1d- and Jα18-deficient mice. In vitro co-culture experiments with alveolar macrophages and NKT cells showed that TNF-α produced by macrophages in the presence of poly[I:C] acts on NKT cells, inducing production of Th2-polarizing cytokines. Moreover, the induction of Th2-polarizing cytokines by poly[I:C] or recombinant TNF-α was impaired in both CD1d- and Jα18-deficient mice and that the above effect was reversed by a TNF-α receptor-2 (TNFR2) blocking peptide, but not by a TNFR1 blocker.
  
  
  CONCLUSIONS
  These findings suggest that NKT cells play a key role in the development of Th2 cell response to inhaled allergens and that TNF-α produced by alveolar macrophages induces Th2 cell response, via TNFR2 on NKT cells.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
authors.forename: J-P
authors.initials: JP
authors.lastname: Choi
authors.forename: Y-M
authors.initials: YM
authors.lastname: Kim
authors.forename: H-I
authors.initials: HI
authors.lastname: Choi
authors.forename: S-J
authors.initials: SJ
authors.lastname: Choi
authors.forename: H T
authors.initials: HT
authors.lastname: Park
authors.forename: W-H
authors.initials: WH
authors.lastname: Lee
authors.forename: Y S
authors.initials: YS
authors.lastname: Gho
authors.forename: Y-K
authors.initials: YK
authors.lastname: Jee
authors.forename: S G
authors.initials: SG
authors.lastname: Jeon
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000485:Allergens; D012330:RNA, Double-Stranded; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha
keywords: TNF receptor-2; TNF-α; Th2 sensitization; dsRNA; type I natural killer T cells