PMID- 23056267
OWN - NLM
STAT- MEDLINE
DCOM- 20130611
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 10
DP  - 2012
TI  - Flt3L combined with rapamycin promotes cardiac allograft tolerance by inducing 
      regulatory dendritic cells and allograft autophagy in mice.
PG  - e46230
LID - 10.1371/journal.pone.0046230 [doi]
LID - e46230
AB  - The induction of immune tolerance is still a formidable challenge in organ 
      transplantation. Dendritic cells (DCs) play an important role in orchestrating 
      immune responses by either mediating protective immune responses or inducing 
      antigen specific tolerance. Previous studies demonstrated that the fms-like 
      tyrosine kinase 3 receptor (Flt3) and its ligand (Flt3L) play an essential role 
      in the regulation of DC commitment and development. Here, we report a synergic 
      effect between Flt3L and low-dose rapamycin (Rapa) in the protection of allograft 
      rejction. It was found that Flt3L combined with Rapa significantly prolonged 
      murine cardiac allograft survival time as compared with that of untreated 
      recipients or recipients treated with Rapa or Flt3L alone. Mechanistic studies 
      revealed that Flt3L combined with low-dose of Rapa induced the generation of 
      tolerogenic DCs along with the production of CD25(+) Foxp3(+) regulatory T cells 
      and IL-10 secretion. We also observed enhanced autophagy in the cardiac 
      allograft, which could be another asset contributing to the enhanced allograft 
      survival. All together, these data suggest that Flt3L combined with low-dose of 
      Rapa could be an effective therapeutic approach to induce tolerance in clinical 
      setting of transplantation.
FAU - Xiong, Ali
AU  - Xiong A
AD  - Department of Immunology, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, Hubei, China.
FAU - Duan, Lihua
AU  - Duan L
FAU - Chen, Jie
AU  - Chen J
FAU - Fan, Zhigang
AU  - Fan Z
FAU - Zheng, Fang
AU  - Zheng F
FAU - Tan, Zheng
AU  - Tan Z
FAU - Gong, Feili
AU  - Gong F
FAU - Fang, Min
AU  - Fang M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121002
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Membrane Proteins)
RN  - 0 (flt3 ligand protein)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Dendritic Cells/*immunology
MH  - Heart Transplantation/*immunology
MH  - *Immune Tolerance
MH  - Membrane Proteins/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Sirolimus/*pharmacology
MH  - Transplantation, Homologous
PMC - PMC3462742
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/12 06:00
MHDA- 2013/06/12 06:00
PMCR- 2012/10/02
CRDT- 2012/10/12 06:00
PHST- 2012/05/11 00:00 [received]
PHST- 2012/08/28 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
PHST- 2012/10/02 00:00 [pmc-release]
AID - PONE-D-12-14092 [pii]
AID - 10.1371/journal.pone.0046230 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(10):e46230. doi: 10.1371/journal.pone.0046230. Epub 2012 Oct 2.