title: Decline of FOXN1 gene expression in human thymus correlates with age: possible epigenetic regulation.
abstract: BACKGROUND
  Thymic involution is thought to be an important factor of age related immunodeficiency. Understanding the molecular mechanisms of human thymic senescence may lead to the discovery of novel therapeutic approaches aimed at the reestablishment of central and peripheral T cell repertoire.
  
  
  RESULTS
  As an initial approach, here we report that the decline of human thymic FOXN1 transcription correlates with age, while other genes, DLL1, DLL4 and WNT4, essential for thymopoiesis, are constitutively transcribed. Using a human thymic epithelial cell line (hTEC), we show that FOXN1 expression is refractory to signals that induce FOXN1 transcription in primary 3D culture conditions and by stimulation of the canonical WNT signaling pathway. Blockage of FOXN1 induceability in the hTEC line may be mediated by an epigenetic mechanism, the CpG methylation of the FOXN1 gene.
  
  
  CONCLUSIONS
  We showed a suppression of FOXN1 transcription both in cultured human thymic epithelial cells and in the aging thymus. We hypothesize that the underlying mechanism may be associated with changes of the DNA methylation state of the FOXN1 gene.
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil ; Department of Human Genetics, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Maria Danielma Dos Santos
authors.initials: MD
authors.lastname: Reis
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Csomos
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Luciene Paschoal Braga
authors.initials: LP
authors.lastname: Dias
authors.affiliation: Gottsegen György Hungarian Institute of Cardiology, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Prodan
authors.affiliation: Department of Cardiac Surgery, Clinical Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Szerafin
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.affiliation: Department of Human Genetics, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary ; Biosystems International Kft, Debrecen, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Takacs