Milk: an exosomal microRNA transmitter promoting thymic regulatory T cell maturation preventing the development of atopy?

Autor(en): Melnik, Bodo C.
John, Swen Malte 
Schmitz, Gerd
Stichwörter: ALDRICH-SYNDROME PROTEIN; Atopy prevention; C-MAF; CHILDHOOD ASTHMA; DNA demethylation; DNA HYPOMETHYLATION; Exosome; EXTRACELLULAR VESICLES; FoxP3; FOXP3 EXPRESSION; IMMUNE-RELATED MICRORNAS; INNATE IMMUNITY; Medicine, Research & Experimental; MicroRNA; Milk; MiR-155; NF-KAPPA-B; Regulatory T cell; Research & Experimental Medicine; TARGET GENES
Erscheinungsdatum: 2014
Herausgeber: BMC
Journal: JOURNAL OF TRANSLATIONAL MEDICINE
Volumen: 12
Zusammenfassung: 
Epidemiological evidence confirmed that raw cow's milk consumption in the first year of life protects against the development of atopic diseases and increases the number of regulatory T-cells (Tregs). However, milk's atopy-protective mode of action remains elusive. This review supported by translational research proposes that milk-derived microRNAs (miRs) may represent the missing candidates that promote long-term lineage commitment of Tregs downregulating IL-4/Th2-mediated atopic sensitization and effector immune responses. Milk transfers exosomal miRs including the ancient miR-155, which is important for the development of the immune system and controls pivotal target genes involved in the regulation of FoxP3 expression, IL-4 signaling, immunoglobulin class switching to IgE and Fc epsilon RI expression. Boiling of milk abolishes milk's exosomal miR-mediated bioactivity. Infant formula in comparison to human breast- or cow's milk is deficient in bioactive exosomal miRs that may impair FoxP3 expression. The boost of milk-mediated miR may induce pivotal immunoregulatory and epigenetic modifications required for long-term thymic Treg lineage commitment explaining the atopy-protective effect of raw cow's milk consumption. The presented concept offers a new option for the prevention of atopic diseases by the addition of physiological amounts of miR-155-enriched exosomes to infant formula for mothers incapable of breastfeeding.
DOI: 10.1186/1479-5876-12-43

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