title: Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes.
abstract: BACKGROUND
  Bronchial asthma is a chronic inflammatory disease resulting from complex gene-environment interactions. Natural microbial exposure has been identified as an important environmental condition that provides asthma protection in a prenatal window of opportunity. Epigenetic regulation is an important mechanism by which environmental factors might interact with genes involved in allergy and asthma development.
  
  
  OBJECTIVE
  This study was designed to test whether epigenetic mechanisms might contribute to asthma protection conferred by early microbial exposure.
  
  
  METHODS
  Pregnant maternal mice were exposed to the farm-derived gram-negative bacterium Acinetobacter lwoffii F78. Epigenetic modifications in the offspring were analyzed in T(H)1- and T(H)2-relevant genes of CD4(+) T cells.
  
  
  RESULTS
  Prenatal administration of A lwoffii F78 prevented the development of an asthmatic phenotype in the progeny, and this effect was IFN-γ dependent. Furthermore, the IFNG promoter of CD4(+) T cells in the offspring revealed a significant protection against loss of histone 4 (H4) acetylation, which was closely associated with IFN-γ expression. Pharmacologic inhibition of H4 acetylation in the offspring abolished the asthma-protective phenotype. Regarding T(H)2-relevant genes only at the IL4 promoter, a decrease could be detected for H4 acetylation but not at the IL5 promoter or the intergenic T(H)2 regulatory region conserved noncoding sequence 1 (CNS1).
  
  
  CONCLUSIONS
  These data support the hygiene concept and indicate that microbes operate by means of epigenetic mechanisms. This provides a new mechanism in the understanding of gene-environment interactions in the context of allergy protection.
authors.affiliation: Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brand
authors.forename: René
authors.initials: R
authors.lastname: Teich
authors.forename: Tanja
authors.initials: T
authors.lastname: Dicke
authors.forename: Hani
authors.initials: H
authors.lastname: Harb
authors.forename: Ali Ö
authors.initials: AÖ
authors.lastname: Yildirim
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Robert A
authors.initials: RA
authors.lastname: Waterland
authors.forename: Uta-Maria
authors.initials: UM
authors.lastname: Bauer
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Petra I
authors.initials: PI
authors.lastname: Pfefferle
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
mesh_terms: D000107:Acetylation; D000150:Acinetobacter / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D007112:Immunity, Maternally-Acquired / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors; D013601:T-Lymphocytes
chemical_list: D006657:Histones