title: TNF-alpha is a key mediator in the development of Th2 cell response to inhaled allergens induced by a viral PAMP double-stranded RNA.
abstract: BACKGROUND
  Viral pathogen-associated molecular patterns, such as dsRNA, disrupt airway tolerance to inhaled allergens. Specifically, the Th2 and Th17 cell responses are induced by low-dose dsRNA and the Th1-dominant response by high-dose dsRNA.
  
  
  OBJECTIVE
  In this model, we evaluate the role of TNF-α in the development of adaptive immune dysfunction to inhaled allergens induced by airway sensitization with dsRNA-containing allergens.
  
  
  METHODS
  A virus-associated asthma mouse model was generated via simultaneous airway administration of ovalbumin (OVA) and low (0.1 μg) or high (10 μg) doses of polyinosine-polycytidylic acid (poly[I:C]). The effect of TNF-α on Th2 airway inflammation was evaluated using TNF-α-deficient mice and recombinant TNF-α.
  
  
  RESULTS
  TNF-α production was enhanced by airway exposure to low and high doses of poly[I:C]. After airway sensitization with OVA plus low-dose poly[I:C], TNF-α-deficient mice exhibited less OVA-induced airway inflammation than did wild-type (WT) mice. However, this did not occur upon sensitization with high-dose poly[I:C]. In terms of T-cell response, the production of IL-4 from lung T cells after OVA challenge was enhanced by airway sensitization with OVA plus low-dose poly[I:C] in WT mice, and this phenotype was inhibited by the absence of TNF-α. Moreover, the Th2 cell response induced by sensitization with OVA plus low-dose poly[I:C], which was abolished in TNF-α-deficient mice, was restored in these mice upon addition of recombinant TNF-α.
  
  
  CONCLUSIONS
  The results of this study suggest that TNF-α produced by airway exposure to low-dose dsRNA is a key mediator in the development of Th2 cell response to inhaled allergens.
authors: Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology, Korea.
authors: J-P
authors: JP
authors: Choi
authors: Y-S
authors: YS
authors: Kim
authors: O Y
authors: OY
authors: Kim
authors: Y-M
authors: YM
authors: Kim
authors: S G
authors: SG
authors: Jeon
authors: T-Y
authors: TY
authors: Roh
authors: J-S
authors: JS
authors: Park
authors: Y S
authors: YS
authors: Gho
authors: Y-K
authors: YK
authors: Kim
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D012330:RNA, Double-Stranded / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D000485:Allergens; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha