title: Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis.
abstract: BACKGROUND
  Hypersensitivity pneumonitis (HP) is mediated by a Th1 immune response. Transcription factor GATA binding protein-3 (GATA-3) is believed to be a key regulator of Th2 differentiation and thus might play regulatory roles in the pathogenesis of hypersensitivity pneumonitis (HP).
  
  
  OBJECTIVE
  We examined the effect of GATA-3 overexpression on the development of HP in mice.
  
  
  METHODS
  Wild-type C57BL/6 mice and GATA-3-overexpressing mice of the same background were used in this study. HP was induced by repeated exposure to Saccharopolyspora rectivirgula, the causative antigen of farmer's lung.
  
  
  RESULTS
  Antigen exposure resulted in a marked inflammatory response with enhanced pulmonary expression of T-bet and the Th1 cytokine interferon (IFN)-gamma in wild-type mice. The degree of pulmonary inflammation was much less severe in GATA-3-overexpressing mice. The induction of T-bet and IFN-gamma genes was suppressed, but a significant induction of Th2 cytokines, including IL-5 and IL-13, was observed in the lungs of GATA-3-overexpressing mice after antigen exposure. Supplementation with recombinant IFN-gamma enhanced lung inflammatory responses in GATA-3-overexpressing mice to the level of wild-type mice. Because antigen-induced IFN-gamma production predominantly occurred in CD4+ T cells, nude mice were transferred with CD4+ T cells from either wild-type or GATA-3-overexpressing mice and subsequently exposed to antigen. Lung inflammatory responses were significantly lower in nude mice transferred with CD4+ T cells from GATA-3-overexpressing mice than in those with wild-type CD4+ T cells, with a reduction of lung IFN-gamma level.
  
  
  CONCLUSIONS
  These results indicate that overexpression of GATA-3 attenuates the development of HP by correcting the Th1-polarizing condition.
authors: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors: Yosuke
authors: Y
authors: Matsuno
authors: Yukio
authors: Y
authors: Ishii
authors: Keigyou
authors: K
authors: Yoh
authors: Yuko
authors: Y
authors: Morishima
authors: Norihiro
authors: N
authors: Haraguchi
authors: Norihiro
authors: N
authors: Kikuchi
authors: Takashi
authors: T
authors: Iizuka
authors: Takumi
authors: T
authors: Kiwamoto
authors: Shinsuke
authors: S
authors: Homma
authors: Akihiro
authors: A
authors: Nomura
authors: Tohru
authors: T
authors: Sakamoto
authors: Morio
authors: M
authors: Ohtsuka
authors: Nobuyuki
authors: N
authors: Hizawa
authors: Satoru
authors: S
authors: Takahashi
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D016930:Saccharopolyspora; D020825:T-Box Domain Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007378:Interleukins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma