title: NFATc1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma.
abstract: BACKGROUND
  NFATc1 isoforms are highly regulated in peripheral T cells where they contribute to the effector function and cell homeostasis.
  
  
  OBJECTIVE
  Here, we investigated the role of NFATc1 in asthma and in T cells.
  
  
  METHODS
  In a murine model of allergic asthma, we analysed differences in T-cell development in this allergic disease model, between wild-type and NFATc1 conditional knockout mice. Thus, we performed quantitative real-time PCR to investigate the mRNA expression of Th2-associated genes as well as genes that are involved in IgE immunoglobulin class-switch. Additionally, we used ELISA, Western blot and flow cytometry (FACS) to analyse protein concentrations of Th1-, Th2- and Th17-specific transcription factors and cytokines and the Th2 chemokine, thymus and activation-regulated chemokine/chemokine ligand 17 (TARC/CCL17) by ELISA.
  
  
  RESULTS
  Mice lacking NFATc1 in CD4(+) T cells display a significant reduction in lung Th2 and Th17 as well as an increase of Th1 cells in an experimental asthma model. Additionally, Batf gene, a recently described transcription factor of the Th2 and Th17 cell differentiation as well as a key T and B transcription factor involved in the IgE immunoglobulin class-switch, was found decreased in the lungs of these mice. As a consequence, serum OVA-specific IgE and IgG1 levels were found significantly decreased after allergen exposure and in the absence of NFATc1 in T cells in experimental allergic asthma.
  
  
  CONCLUSIONS
  Targeting NFATc1 in T lymphocytes ameliorated the allergic trait in the airways of NFATc1(fl/fl) xCD4Cre mice. NFATc1 emerges as a novel target for anti-allergy intervention.
authors: Division of Molecular Pneumology, Department of Anaesthesiology, University Hospital Erlangen, Erlangen, Germany.
authors: S
authors: S
authors: Koch
authors: Division of Molecular Pneumology, Department of Anaesthesiology, University Hospital Erlangen, Erlangen, Germany.
authors: S
authors: S
authors: Reppert
authors: Division of Molecular Pneumology, Department of Anaesthesiology, University Hospital Erlangen, Erlangen, Germany.
authors: S
authors: S
authors: Finotto
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D054414:Chemokine CCL17 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology*; D040641:Quantitative Trait Loci / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D007074:Immunoglobulin G; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D007073:Immunoglobulin E
keywords: IgE; NFATc1; T cells; allergic asthma; atopy