Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy - 05/12/14
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.
Conclusion |
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.
Le texte complet de cet article est disponible en PDF.Key words : Peanut allergy, anaphylaxis mice, offspring, IgE, IL-4, DNA methylation
Abbreviations used : Con A, CPE, CT, foxp3, MLN, NM, O-NM, O-PAM, PAM, PBL
Plan
| Supported by the National Institutes of Health/NCCAM Center for Complementary and Alternative Medicine grant nos. 1R01AT001495-01A1 and 2R01 AT001495-05A2, Food Allergy Education and Research, and the Winston Wolkoff Fund for Integrative Medicine for Allergies and Wellness. |
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| Disclosure of potential conflict of interest: K. Srivastava has received payment for development of educational presentations from Allertein. X.-M. Li has received research support from the National Institutes of Health and Food Allergy Education and Research, consultancy fees from Columbia University, and travel support from Food Allergy Education and Research; has a patent with Herbal Springs; and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 134 - N° 6
P. 1339 - décembre 2014 Retour au numéro
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