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Milk : A postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation

Melnik, Bodo C.; John, Swen Malte; Carrera-Bastos, Pedro LU and Schmitz, Gerd (2016) In Clinical and Translational Allergy 6(1).
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epigenetic, Exosome, FoxO1, FoxP3, MicroRNA, Milk, mTORC1, Probiotics, TGF-β, Treg
in
Clinical and Translational Allergy
volume
6
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85006320720
  • wos:000390115600001
ISSN
2045-7022
DOI
10.1186/s13601-016-0108-9
language
English
LU publication?
yes
id
f8fd46b9-96de-46a6-a315-25b019f37fec
date added to LUP
2017-01-19 14:23:54
date last changed
2017-10-22 05:25:12
@article{f8fd46b9-96de-46a6-a315-25b019f37fec,
  abstract     = {<p>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.</p>},
  articleno    = {18},
  author       = {Melnik, Bodo C. and John, Swen Malte and Carrera-Bastos, Pedro and Schmitz, Gerd},
  issn         = {2045-7022},
  keyword      = {Epigenetic,Exosome,FoxO1,FoxP3,MicroRNA,Milk,mTORC1,Probiotics,TGF-β,Treg},
  language     = {eng},
  month        = {05},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Clinical and Translational Allergy},
  title        = {Milk : A postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation},
  url          = {http://dx.doi.org/10.1186/s13601-016-0108-9},
  volume       = {6},
  year         = {2016},
}