title: Milk: an exosomal microRNA transmitter promoting thymic regulatory T cell maturation preventing the development of atopy?
abstract: 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 FcϵRI 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.
authors: Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Sedanstrasse 115, D-49090 Osnabrück, Germany. melnik@t-online.de.
authors: Bodo C
authors: BC
authors: Melnik
authors: Swen Malte
authors: SM
authors: John
authors: Gerd
authors: G
authors: Schmitz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D035683:MicroRNAs / Q000378:metabolism*; D008892:Milk / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
chemical_list: D035683:MicroRNAs