Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes
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- Angela Montecalvo
- Thomas E. Starzl Transplantation Institute,
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- Adriana T. Larregina
- Immunology,
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- William J. Shufesky
- Thomas E. Starzl Transplantation Institute,
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- Donna Beer Stolz
- Cell Biology,
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- Mara L. G. Sullivan
- Cell Biology,
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- Jenny M. Karlsson
- Cell Biology,
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- Catherine J. Baty
- Cell Biology,
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- Gregory A. Gibson
- Cell Biology,
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- Geza Erdos
- Departments of Dermatology and
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- Zhiliang Wang
- Thomas E. Starzl Transplantation Institute,
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- Jadranka Milosevic
- Division of Pulmonary, Allergy, and Critical Care Medicine, and
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- Olga A. Tkacheva
- Departments of Dermatology and
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- Sherrie J. Divito
- Thomas E. Starzl Transplantation Institute,
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- Rick Jordan
- Bioinformatics Analysis Core, University of Pittsburgh Medical Center, Pittsburgh, PA
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- James Lyons-Weiler
- Bioinformatics Analysis Core, University of Pittsburgh Medical Center, Pittsburgh, PA
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- Simon C. Watkins
- Cell Biology,
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- Adrian E. Morelli
- Thomas E. Starzl Transplantation Institute,
書誌事項
- 公開日
- 2012-01-19
- DOI
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- 10.1182/blood-2011-02-338004
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>Dendritic cells (DCs) are the most potent APCs. Whereas immature DCs down-regulate T-cell responses to induce/maintain immunologic tolerance, mature DCs promote immunity. To amplify their functions, DCs communicate with neighboring DCs through soluble mediators, cell-to-cell contact, and vesicle exchange. Transfer of nanovesicles (< 100 nm) derived from the endocytic pathway (termed exosomes) represents a novel mechanism of DC-to-DC communication. The facts that exosomes contain exosome-shuttle miRNAs and DC functions can be regulated by exogenous miRNAs, suggest that DC-to-DC interactions could be mediated through exosome-shuttle miRNAs, a hypothesis that remains to be tested. Importantly, the mechanism of transfer of exosome-shuttle miRNAs from the exosome lumen to the cytosol of target cells is unknown. Here, we demonstrate that DCs release exosomes with different miRNAs depending on the maturation of the DCs. By visualizing spontaneous transfer of exosomes between DCs, we demonstrate that exosomes fused with the target DCs, the latter followed by release of the exosome content into the DC cytosol. Importantly, exosome-shuttle miRNAs are functional, because they repress target mRNAs of acceptor DCs. Our findings unveil a mechanism of transfer of exosome-shuttle miRNAs between DCs and its role as a means of communication and posttranscriptional regulation between DCs.</jats:p>
収録刊行物
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- Blood
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Blood 119 (3), 756-766, 2012-01-19
American Society of Hematology