Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes
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 exc...
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| Published in | Blood Vol. 119; no. 3; pp. 756 - 766 |
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| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Washington, DC
Elsevier Inc
19.01.2012
Americain Society of Hematology American Society of Hematology |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | Milosevic, Jadranka Tkacheva, Olga A. Jordan, Rick Erdos, Geza Lyons-Weiler, James Morelli, Adrian E. Watkins, Simon C. Larregina, Adriana T. Shufesky, William J. Divito, Sherrie J. Wang, Zhiliang Beer Stolz, Donna Karlsson, Jenny M. Baty, Catherine J. Montecalvo, Angela Gibson, Gregory A. Sullivan, Mara L.G. |
| Author_xml | – sequence: 1 givenname: Angela surname: Montecalvo fullname: Montecalvo, Angela organization: Thomas E. Starzl Transplantation Institute – sequence: 2 givenname: Adriana T. surname: Larregina fullname: Larregina, Adriana T. organization: Departments of Immunology – sequence: 3 givenname: William J. surname: Shufesky fullname: Shufesky, William J. organization: Thomas E. Starzl Transplantation Institute – sequence: 4 givenname: Donna surname: Beer Stolz fullname: Beer Stolz, Donna organization: Departments of Cell Biology – sequence: 5 givenname: Mara L.G. surname: Sullivan fullname: Sullivan, Mara L.G. organization: Departments of Cell Biology – sequence: 6 givenname: Jenny M. surname: Karlsson fullname: Karlsson, Jenny M. organization: Departments of Cell Biology – sequence: 7 givenname: Catherine J. surname: Baty fullname: Baty, Catherine J. organization: Departments of Cell Biology – sequence: 8 givenname: Gregory A. surname: Gibson fullname: Gibson, Gregory A. organization: Departments of Cell Biology – sequence: 9 givenname: Geza surname: Erdos fullname: Erdos, Geza organization: Departments of Dermatology and – sequence: 10 givenname: Zhiliang surname: Wang fullname: Wang, Zhiliang organization: Thomas E. Starzl Transplantation Institute – sequence: 11 givenname: Jadranka surname: Milosevic fullname: Milosevic, Jadranka organization: Division of Pulmonary, Allergy, and Critical Care Medicine, and – sequence: 12 givenname: Olga A. surname: Tkacheva fullname: Tkacheva, Olga A. organization: Departments of Dermatology and – sequence: 13 givenname: Sherrie J. surname: Divito fullname: Divito, Sherrie J. organization: Thomas E. Starzl Transplantation Institute – sequence: 14 givenname: Rick surname: Jordan fullname: Jordan, Rick organization: Bioinformatics Analysis Core, University of Pittsburgh Medical Center, Pittsburgh, PA – sequence: 15 givenname: James surname: Lyons-Weiler fullname: Lyons-Weiler, James organization: Bioinformatics Analysis Core, University of Pittsburgh Medical Center, Pittsburgh, PA – sequence: 16 givenname: Simon C. surname: Watkins fullname: Watkins, Simon C. organization: Departments of Cell Biology – sequence: 17 givenname: Adrian E. surname: Morelli fullname: Morelli, Adrian E. email: morelli@imap.pitt.edu organization: Thomas E. Starzl Transplantation Institute |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25482018$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22031862$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Animals Antigen Presentation Biological and medical sciences Biomarkers - metabolism Cell Communication Cytosol - metabolism Dendritic Cells - cytology Dendritic Cells - metabolism Endosomes - metabolism Exosomes - genetics Exosomes - metabolism Gene Expression Profiling Hematologic and hematopoietic diseases Immunobiology Medical sciences Membrane Fusion Mice MicroRNAs - physiology Oligonucleotide Array Sequence Analysis |
| Title | Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes |
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