Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-beta
| Autor: | Miranda B. Bennink, Peter M. van der Kraan, Marije I. Koenders, Wim B. van den Berg, Mathijs G A Broeren, Peter L E M van Lent, Arjan P. M. van Caam, Bartijn C. H. Pieters, Fons A. J. van de Loo, Onno J. Arntz, Marieke de Vries |
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| Rok vydání: | 2015 |
| Předmět: |
Science
Biology Real-Time Polymerase Chain Reaction Antibodies Statistics Nonparametric Extracellular Vesicles Mice Microscopy Electron Transmission Transforming Growth Factor beta Extracellular Animals Luciferases Multidisciplinary CD63 Tetraspanin 30 Vesicle Macrophages food and beverages Cell Differentiation Transforming growth factor beta Microvesicles In vitro Cell biology Dairying Milk Membrane protein Immunology biology.protein Medicine Nanoparticles Th17 Cells Cattle Female Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] Intracellular Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0121123 (2015) PLoS One, 10 PLoS One, 10, 3 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0121123 |
| Popis: | Contains fulltext : 154821.PDF (Publisher’s version ) (Open Access) 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-beta, and that anti-TGF-beta 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. |
| Databáze: | OpenAIRE |
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