Open AccessMilk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation
Author(s) -
Melnik Bodo C.,
John Swen Malte,
CarreraBastos Pedro,
Schmitz Gerd
Publication year - 2016
Publication title -
clinical and translational allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.979
H-Index - 37
ISSN - 2045-7022
DOI - 10.1186/s13601-016-0108-9
Subject(s) - foxp3 , epigenetics , immunology , milk allergy , regulatory t cell , biology , cellular differentiation , microbiology and biotechnology , thymic stromal lymphopoietin , medicine , t cell , allergy , food allergy , immune system , genetics , il 2 receptor , gene
Background Breastfeeding has protective effects for the development of allergies and atopy. Recent evidence underlines that consumption of unboiled farm milk in early life is a key factor preventing the development of atopic diseases. Farm milk intake has been associated with increased demethylation of FOXP3 and increased numbers of regulatory T cells (Tregs). Thus, the questions arose which components of farm milk control the differentiation and function of Tregs, critical T cell subsets that promote tolerance induction and inhibit the development of allergy and autoimmunity. Findings Based on translational research we identified at least six major signalling pathways that could explain milk's biological role controlling stable FoxP3 expression and Treg differentiation: (1) via maintaining appropriate magnitudes of Akt‐mTORC1 signalling, (2) via transfer of milk fat‐derived long‐chain ω‐3 fatty acids, (3) via transfer of milk‐derived exosomal microRNAs that apparently decrease FOXP3 promoter methylation, (4) via transfer of exosomal transforming growth factor‐β, which induces SMAD2/SMAD3‐dependent FoxP3 expression, (5) via milk‐derived Bifidobacterium and Lactobacillus species that induce interleukin‐10 (IL‐10)‐mediated differentiation of Tregs, and (6) via milk‐derived oligosaccharides that serve as selected nutrients for the growth of bifidobacteria in the intestine of the new born infant. Conclusion Accumulating evidence underlines that milk is a complex signalling and epigenetic imprinting network that promotes stable FoxP3 expression and long‐lasting Treg differentiation, crucial postnatal events preventing atopic and autoimmune diseases.