PMID- 22031862
OWN - NLM
STAT- MEDLINE
DCOM- 20120313
LR  - 20231120
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 119
IP  - 3
DP  - 2012 Jan 19
TI  - Mechanism of transfer of functional microRNAs between mouse dendritic cells via 
      exosomes.
PG  - 756-66
LID - 10.1182/blood-2011-02-338004 [doi]
AB  - 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.
FAU - Montecalvo, Angela
AU  - Montecalvo A
AD  - Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical 
      Center, PA, USA.
FAU - Larregina, Adriana T
AU  - Larregina AT
FAU - Shufesky, William J
AU  - Shufesky WJ
FAU - Stolz, Donna Beer
AU  - Stolz DB
FAU - Sullivan, Mara L G
AU  - Sullivan ML
FAU - Karlsson, Jenny M
AU  - Karlsson JM
FAU - Baty, Catherine J
AU  - Baty CJ
FAU - Gibson, Gregory A
AU  - Gibson GA
FAU - Erdos, Geza
AU  - Erdos G
FAU - Wang, Zhiliang
AU  - Wang Z
FAU - Milosevic, Jadranka
AU  - Milosevic J
FAU - Tkacheva, Olga A
AU  - Tkacheva OA
FAU - Divito, Sherrie J
AU  - Divito SJ
FAU - Jordan, Rick
AU  - Jordan R
FAU - Lyons-Weiler, James
AU  - Lyons-Weiler J
FAU - Watkins, Simon C
AU  - Watkins SC
FAU - Morelli, Adrian E
AU  - Morelli AE
LA  - eng
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - R01 HL077545/HL/NHLBI NIH HHS/United States
GR  - F30 DK082131/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - R01AI077511/AI/NIAID NIH HHS/United States
GR  - R01 AI077511/AI/NIAID NIH HHS/United States
GR  - R01 HL075512/HL/NHLBI NIH HHS/United States
GR  - HL077545/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111026
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Biomarkers)
RN  - 0 (MicroRNAs)
SB  - IM
CIN - Blood. 2012 Jan 19;119(3):646-8. PMID: 22262739
CIN - Blood. 2012 May 31;119(22):5330-2. PMID: 22653957
MH  - Animals
MH  - Antigen Presentation
MH  - Biomarkers/metabolism
MH  - *Cell Communication
MH  - Cytosol/metabolism
MH  - Dendritic Cells/cytology/*metabolism
MH  - Endosomes/*metabolism
MH  - Exosomes/*genetics/metabolism
MH  - Gene Expression Profiling
MH  - Membrane Fusion
MH  - Mice
MH  - MicroRNAs/*physiology
MH  - Oligonucleotide Array Sequence Analysis
PMC - PMC3265200
EDAT- 2011/10/28 06:00
MHDA- 2012/03/14 06:00
PMCR- 2013/01/19
CRDT- 2011/10/28 06:00
PHST- 2011/10/28 06:00 [entrez]
PHST- 2011/10/28 06:00 [pubmed]
PHST- 2012/03/14 06:00 [medline]
PHST- 2013/01/19 00:00 [pmc-release]
AID - S0006-4971(20)40934-6 [pii]
AID - 2011/338004 [pii]
AID - 10.1182/blood-2011-02-338004 [doi]
PST - ppublish
SO  - Blood. 2012 Jan 19;119(3):756-66. doi: 10.1182/blood-2011-02-338004. Epub 2011 
      Oct 26.