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Cited by 1,429Extracellular vesicles in diseaseMicroRNA in disease regulationCellular transport and secretion

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Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.

Open access
Montecalvo, Angela, Larregina, Adriana T., Shufesky, William J., Beer Stolz, Donna, Sullivan, Mara L. G., Karlsson, Jenny M., Baty, Catherine J., Gibson, Gregory A., Erdos, Geza, Wang, Zhiliang, Milosevic, Jadranka, Tkacheva, Olga A., Divito, Sherrie J., Jordan, Rick, Lyons-Weiler, James, Watkins, Simon C., Morelli, Adrian E.·2012·Blood
DOI 10.1182/blood-2011-02-338004PMC PMC3265200
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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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Crossref · 10.1182/blood-2011-02-338004

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  • Dendritic cells communicate with neighboring cells through soluble mediators, cell-to-cell-contact and vesicle exchange.

    “Dendritic cells are sentinel antigen-presenting cells of the immune system that are known to communicate with neighboring cells through soluble mediators, cell-to-cell-contact and vesicle exchange (Montecalvo et al., 2012) and via release of a vast number of EVs.”

    From Engineered Extracellular Vesicles Loaded With miR-124 Attenuate Cocaine-Mediated Activation of Microglia (2020) · cites this paper as Montecalvo et al., 2012

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Metadata

Authors
Montecalvo, A., Larregina, A. T., Shufesky, W. J., Beer Stolz, D., Sullivan, M. L. G., Karlsson, J. M., Baty, C. J., Gibson, G. A., Erdos, G., Wang, Z., Milosevic, J., Tkacheva, O. A., Divito, S. J., Jordan, R., Lyons-Weiler, J., Watkins, S. C., & Morelli, A. E.
Affiliations
  • Thomas E. Starzl Transplantation Institute,
  • McGowan Institute for Regenerative Medicine (US)
  • Cell Biology,
  • Departments of Dermatology and
  • Division of Pulmonary, Allergy, and Critical Care Medicine, and
  • University of Pittsburgh Medical Center (US)
  • Bioinformatics Analysis Core, University of Pittsburgh Medical Center, Pittsburgh, PA
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2012-01-19
Volume
119
Issue
3
Pages
756-766
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2011-02-338004
PMC
PMC3265200
OpenAlex
W2111560326
Cited by
1,429
References
5
Citations by year
2026: 35 · 2025: 62 · 2024: 79 · 2023: 93 · 2022: 118 · 2021: 124 · 2020: 125 · 2019: 118 · 2018: 117 · 2017: 112 · 2016: 113 · 2015: 89 · 2014: 106 · 2013: 82 · 2012: 54
FWCI
25.89
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (UL1TR000005)
  • National Heart, Lung, and Blood Institute (R01HL077545, R01HL075512)
  • National Institute of Allergy and Infectious Diseases (R01AI077511)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F30DK082131)
  • National Center for Research Resources (UL1RR024153)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
dendritic cells, exosomes, microRNA, dendritic cell maturation, post-transcriptional regulation, antigen presentation, immune tolerance
MeSH terms
Animals, Cell Communication, Cytosol, Dendritic Cells, Membrane Fusion, Endosomes, Biomarkers, Antigen Presentation, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, Mice, Exosomes

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