Epigenetic features of FoxP3 in children with cow's milk allergy

Lorella Paparo, Rita Nocerino, Linda Cosenza, Rosita Aitoro, Valeria D'Argenio, Valentina Del Monaco, Carmen Di Scala, Antonio Amoroso, Margherita Di Costanzo, Francesco Salvatore, Roberto Berni Canani, Lorella Paparo, Rita Nocerino, Linda Cosenza, Rosita Aitoro, Valeria D'Argenio, Valentina Del Monaco, Carmen Di Scala, Antonio Amoroso, Margherita Di Costanzo, Francesco Salvatore, Roberto Berni Canani

Abstract

Background: DNA methylation of the Th1 and Th2 cytokine genes is altered during cow's milk allergy (CMA). Forkhead box transcription factor 3 (FoxP3) is essential for the development and function of regulatory T cells (Tregs) and is involved in oral tolerance acquisition. We assessed whether tolerance acquisition in children with IgE-mediated CMA is associated with DNA demethylation of the Treg-specific demethylated region (TSDR) of FoxP3.

Results: Forty children (aged 3-18 months) were enrolled: 10 children with active IgE-mediated CMA (group 1), 10 children who outgrew CMA after dietary treatment with an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (group 2), 10 children who outgrew CMA after treatment with other formulas (group 3), and 10 healthy controls (group 4). FoxP3 TSDR demethylation and expression were measured in mononuclear cells purified from peripheral blood of the four groups of children. FoxP3 TSDR demethylation was significantly lower in children with active IgE-mediated CMA than in either children who outgrew CMA or in healthy children. Formula selection influenced the FoxP3 TSDR demethylation profile. The FoxP3 TSDR demethylation rate and expression level were correlated.

Conclusions: Tolerance acquisition in children with IgE-mediated CMA involves epigenetic regulation of the FoxP3 gene. This feature could be a new target for preventive and therapeutic strategies against CMA.

Trial registration: ClinicalTrials.gov NCT02779881.

Keywords: Extensively hydrolyzed casein formula; Food allergy; Lactobacillus rhamnosus GG; Oral tolerance.

Figures

Fig. 1
Fig. 1
FoxP3 TSDR demethylation rate (%) (a) and FoxP3 mRNA expression versus GUS expression (b) observed in study groups (group 1, CMA children at diagnosis; group 2, children outgrown CMA after treatment with EHCF + LGG; group 3, children outgrown CMA after treatment with other formulas; group 4, healthy controls)
Fig. 2
Fig. 2
Linear regression analysis of % FoxP3 TSDR demethylation rate (%) in PBMCs versus FoxP3 mRNA expression in study subjects

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Source: PubMed

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