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- Melnik, Bodo C., et al.
(författare)
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Milk : A postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation
- 2016
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1
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Forskningsöversikt (refereegranskat)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 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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| 2. |
- Melnik, Bodo C., et al.
(författare)
-
Milk miRNAs : Simple nutrients or systemic functional regulators?
- 2016
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Ingår i: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Milk is rich in miRNAs that appear to play important roles in the postnatal development of all mammals. Currently, two competing hypotheses exist: the functional hypothesis, which proposes that milk miRNAs are transferred to the offspring and exert physiological regulatory functions, and the nutritional hypothesis, which suggests that these molecules do not reach the systemic circulation of the milk recipient, but merely provide nutrition without conferring active regulatory signals to the offspring. The functional hypothesis is based on indirect evidence and requires further investigation. The nutritional hypothesis is primarily based on three mouse models, which are inherently problematic: 1) miRNA-375 KO mice, 2) miRNA-200c/141 KO mice, and 3) transgenic mice presenting high levels of miRNA-30b in milk. This article presents circumstantial evidence that these mouse models may all be inappropriate to study the physiological traffic of milk miRNAs to the newborn mammal, and calls for new studies using more relevant mouse models or human milk to address the fate and role of milk miRNAs in the offspring and the adult consumer of cow's milk.
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