PMID- 25558978
OWN - NLM
STAT- MEDLINE
DCOM- 20150509
LR  - 20150312
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 128
IP  - 10
DP  - 2015 May 1
TI  - Activated regulatory T-cells attenuate myocardial ischaemia/reperfusion injury 
      through a CD39-dependent mechanism.
PG  - 679-93
LID - 10.1042/CS20140672 [doi]
AB  - Regulatory T-cells (Tregs) are generally regarded as key immunomodulators that 
      maintain immune tolerance and counteract tissue damage in a variety of 
      immune-mediated disorders. However, its role in myocardial ischaemia/reperfusion 
      injury (MIRI) remains unknown. The purpose of the present study was to determine 
      whether Tregs exert a beneficial effect on mouse MIRI. We examined the role of 
      Tregs in murine MIRI by depletion using 'depletion of regulatory T-cell' (DEREG) 
      mice and adoptive transfer using Forkhead box P3 (Foxp3)-GFP knockin mice and the 
      mechanisms of cardio protection were further studied in vivo and in vitro. Tregs 
      rapidly accumulated in murine hearts following MIRI. Selective depletion of Tregs 
      in the DEREG mouse model resulted in aggravated MIRI. In contrast, the adoptive 
      transfer of in vitro-activated Tregs suppressed MIRI, whereas freshly isolated 
      Tregs had no effect. Mechanistically, activated Treg-mediated protection against 
      MIRI was not abrogated by interleukin (IL)-10 or transforming growth factor 
      (TGF)-beta1 inhibition but was impaired by the genetic deletion of cluster of 
      differentiation 39 (CD39). Moreover, adoptive transfer of in vitro-activated 
      Tregs attenuated cardiomyocyte apoptosis, activated a pro-survival pathway 
      involving Akt and extracellular-signal-regulated kinase (ERK) and inhibited 
      neutrophil infiltration, which was compromised by CD39 deficiency. Finally, the 
      peripheral blood mononuclear cells of acute myocardial infarction (AMI) patients 
      after primary percutaneous coronary intervention (PCI) revealed a decrease in 
      CD4+CD25+CD127low Tregs and a relative increase in CD39+ cells within the Treg 
      population. In conclusion, our data validated a protective role for Tregs in 
      MIRI. Moreover, in vitro-activated Tregs ameliorated MIRI via a CD39-dependent 
      mechanism, representing a putative therapeutic strategy.
FAU - Xia, Ni
AU  - Xia N
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Jiao, Jiao
AU  - Jiao J
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Tang, Ting-Ting
AU  - Tang TT
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Lv, Bing-Jie
AU  - Lv BJ
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Lu, Yu-Zhi
AU  - Lu YZ
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Wang, Ke-Jing
AU  - Wang KJ
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Zhu, Zheng-Feng
AU  - Zhu ZF
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Mao, Xiao-Bo
AU  - Mao XB
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Nie, Shao-Fang
AU  - Nie SF
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Wang, Qing
AU  - Wang Q
AD  - daggerCenter for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner 
      Research Institute, Cleveland Clinic, Cleveland, OH 44195, U.S.A.
FAU - Tu, Xin
AU  - Tu X
AD  - double daggerKey Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X 
      Institute, College of Life Science and Technology and Center of Human Genome 
      Research, Huazhong University of Science and Technology, Wuhan 430074, China.
FAU - Xiao, Hong
AU  - Xiao H
AD  -  section signDepartment of Scientific Research, The 4th Hospital of Wuhan, Wuhan 430000, 
      China.
FAU - Liao, Yu-Hua
AU  - Liao YH
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
FAU - Shi, Guo-Ping
AU  - Shi GP
AD  -  paragraph signDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA 02115, U.S.A.
FAU - Cheng, Xiang
AU  - Cheng X
AD  - *Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union 
      Hospital, Tongji Medical College of Huazhong University of Science and 
      Technology; Laboratory of Biological Targeted Therapy of the Ministry of 
      Education, Wuhan 430022, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Antigens, CD)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 3.6.1.5 (Apyrase)
RN  - EC 3.6.1.5 (CD39 antigen)
SB  - IM
MH  - Adoptive Transfer/methods
MH  - Analysis of Variance
MH  - Animals
MH  - Antigens, CD/*metabolism
MH  - Apyrase/*metabolism
MH  - Forkhead Transcription Factors/genetics
MH  - Gene Knock-In Techniques
MH  - Green Fluorescent Proteins/genetics
MH  - Immunotherapy/*methods
MH  - Lymphocyte Activation/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Reperfusion Injury/*immunology
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
EDAT- 2015/01/07 06:00
MHDA- 2015/05/10 06:00
CRDT- 2015/01/07 06:00
PHST- 2015/01/07 06:00 [entrez]
PHST- 2015/01/07 06:00 [pubmed]
PHST- 2015/05/10 06:00 [medline]
AID - CS20140672 [pii]
AID - 10.1042/CS20140672 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2015 May 1;128(10):679-93. doi: 10.1042/CS20140672.