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Table 1 Translational evidence for milk-microRNA-mediated thymic Treg maturation

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

Potential function of milk microRNA Comment References
Milk contains abundant miRs From all body fluids human milk contains the highest amounts of RNAs and miRs [7882, 8487, 92]
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 [7981, 84, 85, 87]
The majority of milk’s miRs are transported in exosomes Exosomes transfer genetic information for cell-cell communications over short and long distances [81, 82, 8487, 92]
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 [84, 85]
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 [80, 81, 86]
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 [94, 95]
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 [82, 85, 92]
Exosomal transfer is a known mechanism of communication between immune cells Macrophages, B-cell, T cells and thymocytes communicate via exosome transfer [7073, 91]
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 [74, 91]
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 [74, 91]
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 [105, 106]