title: The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune responses in the setting of allergic asthma.
abstract: BACKGROUND
  Mice without the basic leucine zipper transcription factor, ATF-like (BATF) gene (Batf(-/-)) lack TH17 and follicular helper T cells, which demonstrates that Batf is a transcription factor important for T- and B-cell differentiation.
  
  
  OBJECTIVE
  In this study we examined whether BATF expression would influence allergic asthma.
  
  
  METHODS
  In a cohort of preschool control children and children with asthma, we analyzed BATF mRNA expression using real-time PCR in PBMCs. In a murine model of allergic asthma, we analyzed differences in this allergic disease between wild-type, Batf transgenic, and Batf(-/-) mice.
  
  
  RESULTS
  In the absence of corticosteroid treatment, children with recurrent asthma have a significant increase in BATF mRNA expression in their PBMCs. Batf(-/-) mice display a significant reduction in the pathophysiologic responses seen in asthmatic wild-type littermates. Moreover, we discovered a decrease in IL-3 production and IL-3-dependent mast cell development in Batf(-/-) mice. By contrast, IFN-γ was induced in lung CD4(+) and CD8(+) T cells. Intranasal delivery of anti-IFN-γ antibodies induced airway hyperresponsiveness and inflammation in wild-type but not in Batf(-/-) mice. Transgenic overexpression of Batf under the control of the CD2 promoter/enhancer augmented lung inflammation and IgE levels in the setting of experimental asthma.
  
  
  CONCLUSIONS
  BATF is increased in non-steroid-treated asthmatic children. Targeting BATF expression resulted in amelioration of the pathophysiologic responses seen in children with allergic asthma, and BATF has emerged as a novel target for antiasthma interventions.
authors.affiliation: Department of Molecular Pneumology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Übel
authors.affiliation: Department of Molecular Pneumology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Sopel
authors.affiliation: Department of Molecular Pneumology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Graser
authors.affiliation: Department of Medicine I, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Hildner
authors.affiliation: Department of Allergy and Pneumology, Children's Hospital, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Reinhardt
authors.affiliation: Department of Allergy and Pneumology, Children's Hospital, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Theodor
authors.initials: T
authors.lastname: Zimmermann
authors.affiliation: Institute of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Ralf Joachim
authors.initials: RJ
authors.lastname: Rieker
authors.affiliation: Department of Molecular Pneumology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Maier
authors.affiliation: Department of Medicine I, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.affiliation: Department of Pathology, Washington University, St Louis, Mo.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Department of Molecular Pneumology, University of Erlangen-Nürnberg, Erlangen, Germany. Electronic address: susetta.finotto@uk-erlangen.de.
authors.forename: Susetta
authors.initials: S
authors.lastname: Finotto
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001249:Asthma / Q000276:immunology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D019076:Transgenes / Q000235:genetics; D015854:Up-Regulation
chemical_list: D019138:Antibodies, Blocking; C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D007377:Interleukin-3; D012333:RNA, Messenger; D007073:Immunoglobulin E; D007371:Interferon-gamma
keywords: AHR; ATF; Activating transcription factor; Airway hyperresponsiveness; BAL; BALF; BATF; BMMC; Basic leucine zipper transcription factor, ATF-like; Bone marrow–derived mast cell; Bronchoalveolar lavage; Bronchoalveolar lavage fluid; Enhanced pause; Forkhead box protein 3; Foxp3; IRF4; Interferon regulatory factor 4; MCh; Methacholine; OVA; Ovalbumin; P(enh); Phospho–signal transducer and activator of transcription 5; RORγt; Regulatory T; Retinoic acid–related orphan receptor γt; SCF; STAT; Signal transducer and activator of transcription; Stem cell factor; T cells; T(H)17; T(H)2; T-bet; T-box transcription factor; Treg; asthma; mast cells; pSTAT5