Melnik, Bodo C. and John, Swen Malte and Carrera-Bastos, Pedro and Schmitz, Gerd (2016) Milk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation. CLINICAL AND TRANSLATIONAL ALLERGY, 6: 18. ISSN 2045-7022
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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.-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-beta, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DNA METHYLTRANSFERASE 1; COWS MILK; TGF-BETA; ALLERGIC DISEASE; GENE-EXPRESSION; CHILDHOOD ASTHMA; MESSENGER-RNA; BREAST-MILK; AMINO-ACIDS; LACTOBACILLUS-ACIDOPHILUS; Epigenetic; Exosome; FoxO1; FoxP3; Milk; MicroRNA; mTORC1; Probiotics; TGF-beta; Treg |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Petra Gürster |
| Date Deposited: | 02 Sep 2020 06:20 |
| Last Modified: | 02 Sep 2020 06:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2936 |
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