Introduction
Atopic diseases are associated with reduced Treg numbers
Thymic maturation of natural regulatory T cells
Role of microRNAs in thymic FoxP3+ Treg cell maturation
Exosomal microRNAs in immune cell communication
Milk-derived exosomal miRs: boosters for thymic Treg maturation?
Milk exosome CD81: an exosomal antigen required for thymocyte maturation?
Milk- and thymus-derived exosomes promote Treg maturation
MiR-mediated FOXP3 demethylation
MiR-155 and atopy-related target genes
Increased maternal LPS-exposure during farming enhances miR-155 release
Bioactive exosomal miR-155 in raw cow’s milk
Breastfeeding of non-atopic versus atopic mothers and Treg maturation
Artificial formula feeding and Treg maturation
Conclusion
Potential function of milk microRNA | Comment | References |
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Milk contains abundant miRs | From all body fluids human milk contains the highest amounts of RNAs and miRs | |
Milk contains miR-155, miR-146a, and miR-21 | MiR-155, miR-146a and miR-21 are crucial miRs involved in Treg maturation and function | |
The majority of milk’s miRs are transported in exosomes | Exosomes transfer genetic information for cell-cell communications over short and long distances | |
MiR-155 is a component of colostrum and bovine whey and is found to be transported in exosomes | MiR-155 is an ancient highly conserved miR involved in immune regulation | |
Milk exosomes are resistant against RNase-degradation and acidic conditions (pH1-2) | Milk exosomes may survive the acidic environment of the stomach. Boiling of milk destroys the biological activity of milk miRs | |
Mir-155, miR-146a and miR-21 are components of human blood plasma | Milk miR-containing exosomes may be transported in circulation and may reach the thymus | |
Bovine colostrum and bovine milk and human breast milk exosomes containing miRs are taken up by cells and increase cytoplasmic miR levels | Milk-derived miRs may be taken up by exosome endocytosis in recipient cells. Physical destruction of exosomal lipid bilayer structure abolishes cellular miR uptake | |
Exosomal transfer is a known mechanism of communication between immune cells | Macrophages, B-cell, T cells and thymocytes communicate via exosome transfer | |
Human breast milk exosomes when added to PBMCs induce FoxP3+ Tregs | Breast milk miR-155 may induce the expression of FoxP3+ by inhibiting SOCS1 signaling | [82] |
Exosomes have been detected in the murine and human thymus | Milk-derived exosomes may augment Treg cell maturation in the thymus | |
Murine thymic exosomes when added to thymus CD4+CD25- T cells induce CD4+CD25+FoxP3+ Treg cells | Milk-derived exosomes may promote Treg cell formation of developing thymocytes within the human thymic medulla | |
MiR-21 and miR-29b inhibit DNMT1 expression in T cells | Milk miR-21 and miR-29b may promote stable expression of demethylated FoxP3 and thus lineage commitment of thymic Treg cells |