title: Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy.
abstract: BACKGROUND
  Although maternal atopy is a risk factor for the development of peanut allergy, this phenomenon has not been well characterized experimentally, and the mechanisms underlying offspring risk are unclear.
  
  
  OBJECTIVE
  We sought to determine whether offspring of mothers with peanut allergy (O-PAM mice) are more susceptible to peanut allergy than offspring of naive mothers (O-NM mice) in a murine model and, if so, whether the susceptibility is linked to TH2-biased epigenetic alterations.
  
  
  METHODS
  Five-week-old O-PAM and O-NM mice were intragastrically sensitized to and challenged with peanut. Serum peanut-specific IgE levels, plasma histamine levels, anaphylactic reactions, and splenocyte and MLN cell cytokine production were measured. DNA methylation levels of the Il4 gene promoter from splenocytes and MLN cells from sensitized offspring and splenocytes from unsensitized neonatal offspring were determined by means of pyrosequencing.
  
  
  RESULTS
  O-PAM mice exhibited 3-fold higher peanut-specific IgE levels after peanut sensitization, as well as 5-fold higher histamine levels and significantly higher anaphylactic symptom scores after challenge than O-NM mice (P < .05-.01). Cultured splenocytes and MLNs from O-PAM mice produced significantly more TH2 cytokines than cells from O-NM mice (P < .05-.01). Cells from O-PAM mice exhibited significantly reduced DNA methylation at CpG sites of the Il4 gene promoter than cells from O-NM mice. DNA methylation levels were inversely correlated with IL-4 and IgE production. O-PAM neonatal splenocyte hypomethylation of the Il4 gene promoter was also present.
  
  
  CONCLUSIONS
  This study is the first to demonstrate that increased susceptibility to peanut allergy in O-PAM mice is associated with epigenetic alteration of the Il4 gene promoter. This finding might provide insight into preventing the development of early-life allergy.
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Changda
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Hui
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Kamal
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY; Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Columbia University, New York, NY; Division of Allergy and Immunology, Department of Pediatrics, Columbia University, New York, NY; Department of Environmental Health Sciences, Columbia University, New York, NY.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Miller
authors.affiliation: Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio; Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: xiu-min.li@mssm.edu.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D000818:Animals; D010367:Arachis / Q000009:adverse effects / Q000276:immunology; D018899:CpG Islands; D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D019175:DNA Methylation; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E
keywords: DNA methylation; IL-4; IgE; Peanut allergy; anaphylaxis mice; offspring