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2015 ; 10
(3
): e0121123
Nephropedia Template TP
Pieters BC
; Arntz OJ
; Bennink MB
; Broeren MG
; van Caam AP
; Koenders MI
; van Lent PL
; van den Berg WB
; de Vries M
; van der Kraan PM
; van de Loo FA
PLoS One
2015[]; 10
(3
): e0121123
PMID25822997
show ga
SCOPE: Extracellular vesicles, including exosomes, have been identified in all
biological fluids and rediscovered as an important part of the intercellular
communication. Breast milk also contains extracellular vesicles and the proposed
biological function is to enhance the antimicrobial defense in newborns. It is,
however, unknown whether extracellular vesicles are still present in commercial
milk and, more importantly, whether they retained their bioactivity. Here, we
characterize the extracellular vesicles present in semi-skimmed cow milk
available for consumers and study their effect on T cells. METHODS AND RESULTS:
Extracellular vesicles from commercial milk were isolated and characterized.
Milk-derived extracellular vesicles contained several immunomodulating miRNAs and
membrane protein CD63, characteristics of exosomes. In contrast to RAW 267.4
derived extracellular vesicles the milk-derived extracellular vesicles were
extremely stable under degrading conditions, including low pH, boiling and
freezing. Milk-derived extracellular vesicles were easily taken up by murine
macrophages in vitro. Furthermore, we found that they can facilitate T cell
differentiation towards the pathogenic Th17 lineage. Using a (CAGA)12-luc
reporter assay we showed that these extracellular vesicles carried bioactive
TGF-?, and that anti-TGF-? antibodies blocked Th17 differentiation. CONCLUSION:
Our findings show that commercial milk contains stable extracellular vesicles,
including exosomes, and carry immunoregulatory cargo. These data suggest that the
extracellular vesicles present in commercial cow milk remains intact in the
gastrointestinal tract and exert an immunoregulatory effect.