title: Intranasal delivery of T-bet modulates the profile of helper T cell immune responses in experimental asthma.
abstract: BACKGROUND
  Allergic asthma is caused by aberrant helper T (T(H)) type 2 immune responses in susceptible individuals, characterized by airway hyperresponsiveness, chronic airway inflammation, and mucus hypersecretion. Its prevalence continues to increase, but optimal treatment remains a challenge. The transcription factor T-bet is a master regulator of T(H)1 lineage commitment and strongly promotes interferon gamma expression during T(H)1 cell differentiation.
  
  
  OBJECTIVE
  The aim of this study was to explore the role of intranasal delivery of T-bet on the differentiation of T(H) cell subsets and airway inflammation in the ovalbumin (OVA)-induced mouse model of allergic airway inflammation.
  
  
  METHODS
  BALB/c mice were sensitized by intraperitoneal injection of OVA and challenged with nebulized OVA. Four days before the inhalation challenge, the sensitized mice were subjected to intranasal delivery of a recombinant adeno-associated virus vector carrying murine T-bet gene (AAV-T-bet). Expression of the transcription factors T-bet, GATA3, and Foxp3 was then assayed in the lungs, and airway histology was analyzed along with other inflammatory parameters, such as eosinophils and cytokines in bronchoalveolar lavage (BAL) fluid, and total and OVA-specific immunoglobulin (Ig) E in serum.
  
  
  RESULTS
  Intranasal administration of AAV-T-bet efficiently balanced the T(H)1/T(H)2 transcription factor and cytokine profile and significantly decreased the number of eosinophils in BAL fluid. It also resulted in a reduction of peribronchial inflammation scores and serum IgE levels in OVA-sensitized and challenged mice during the effector phase.
  
  
  CONCLUSIONS
  Our data show that intranasal delivery of T-bet can promote a T(H)1 immune response, restore a balanced Th immune response, and inhibit airway inflammation during the challenge phase in a mouse model of allergic airway inflammation.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: X P
authors.initials: XP
authors.lastname: Xu
authors.forename: G F
authors.initials: GF
authors.lastname: Qiu
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: S J
authors.initials: SJ
authors.lastname: Wang
authors.forename: X X
authors.initials: XX
authors.lastname: Huang
authors.forename: H X
authors.initials: HX
authors.lastname: Xu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D007114:Immunization; D007167:Immunotherapy; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D010047:Ovalbumin