title: Restoration of T-box-containing protein expressed in T cells protects against allergen-induced asthma.
abstract: BACKGROUND
  A T(H)1-specific transcription factor, T-box-containing protein expressed in T cells (T-bet), controls the production of both T(H)1 and T(H)2 cytokines in T(H) cell differentiation by means of distinct mechanisms. T-bet-deficient mice overproduce T(H)2 cytokines and have spontaneous airway inflammation.
  
  
  OBJECTIVE
  We tested whether T-bet overexpression could protect against the development or progression of asthma.
  
  
  METHODS
  We generated a T cell-specific and inducible line of T-bet-transgenic mice on a T-bet-deficient genetic background and used it to study the function of T-bet in an ovalbumin (OVA)-induced asthma model.
  
  
  RESULTS
  Induction of T-bet in a T cell-specific manner in an OVA model of asthma concomitant with OVA injection prevented airway hyperresponsiveness, eosinophilic and lymphocytic inflammation, and IL-5 and IL-13 production in bronchoalveolar lavage fluid and also reduced serum IgE and T(H)2 cytokine production by peripheral T cells. Even when T-bet expression was induced during later stages of asthma progression, T-bet overexpression still attenuated airway hyperresponsiveness and goblet cell hyperplasia, as well as T(H)2 cytokine production.
  
  
  CONCLUSIONS
  Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma.
authors.affiliation: Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Min
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Hong
authors.forename: Kirsten S
authors.initials: KS
authors.lastname: Sigrist
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D000485:Allergens; D016207:Cytokines; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007073:Immunoglobulin E; D010047:Ovalbumin; D004318:Doxycycline