Milk : A postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation
(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.
(Less)
- author
- Melnik, Bodo C. ; John, Swen Malte ; Carrera-Bastos, Pedro LU and Schmitz, Gerd
- organization
- publishing date
- 2016-05-12
- 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
- article number
- 18
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85006320720
- pmid:27175277
- 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
- 2024-05-03 18:30:29
@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>}},
author = {{Melnik, Bodo C. and John, Swen Malte and Carrera-Bastos, Pedro and Schmitz, Gerd}},
issn = {{2045-7022}},
keywords = {{Epigenetic; Exosome; FoxO1; FoxP3; MicroRNA; Milk; mTORC1; Probiotics; TGF-β; Treg}},
language = {{eng}},
month = {{05}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
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}},
doi = {{10.1186/s13601-016-0108-9}},
volume = {{6}},
year = {{2016}},
}