title: TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA.
abstract: BACKGROUND
  Although respiratory viral infections in early childhood can enhance the development of airway allergen sensitization, the exact mechanisms of the effects of viral infections on the adaptive immune response to inhaled allergens are controversial.
  
  
  OBJECTIVE
  We sought to evaluate the effects of double-stranded RNA (dsRNA) on airway sensitization to inhaled allergens.
  
  
  METHODS
  Novel mouse models were created through simultaneous airway sensitization to an allergen and low or high doses of dsRNA. The mouse models were applied to Toll-like receptor 3-, IL-13-, IL-4-, signal transducer and activator of transcription (STAT) 6-, IFN-gamma-, and T-box expressed in T cells (T-bet)-deficient mice to evaluate underlying pathophysiologic mechanisms in the development of allergic lung inflammation.
  
  
  RESULTS
  We found that airway allergen sensitization with dsRNA induced lung inflammation that was not present in Toll-like receptor 3-deficient mice. Moreover, lung inflammation enhanced by low-dose dsRNA was impaired in IL-13-deficient mice, whereas lung inflammation by high-dose dsRNA was impaired in IFN-gamma-deficient mice. The models also demonstrated that low-dose dsRNA enhanced IL-4 expression during allergen sensitization and that inflammation enhanced by low-dose dsRNA was not present in IL-4- or STAT6-deficient mice. In contrast, the present study showed that high-dose dsRNA enhanced IFN-gamma expression during allergen sensitization and that the development of lung inflammation enhanced by high-dose dsRNA was impaired in T-bet-deficient mice.
  
  
  CONCLUSIONS
  These findings suggest that airway allergen exposure during respiratory viral infections might induce asthma induced by both T(H)1 and T(H)2 immune responses to inhaled allergens.
  
  
  CONCLUSIONS
  Targeting both T(H)1 and T(H)2 lung inflammation might be important in the treatment of virus-associated asthma.
authors.affiliation: Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Oh
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Park
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Shim
authors.forename: Hyun-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Oh
authors.forename: Boram
authors.initials: B
authors.lastname: Bang
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Chun
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.forename: You-Young
authors.initials: YY
authors.lastname: Kim
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000209:etiology*; D016535:Bronchial Hyperreactivity / Q000209:etiology; D007371:Interferon-gamma / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011070:Poly I-C / Q000008:administration & dosage*; D012330:RNA, Double-Stranded / Q000008:administration & dosage*; D050800:STAT6 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000502:physiology
chemical_list: D000485:Allergens; D018793:Interleukin-13; D012330:RNA, Double-Stranded; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D011070:Poly I-C