PMID- 29459719
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20191210
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 3
DP  - 2018 Feb 19
TI  - miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory 
      T cell (tTreg).
PG  - 290
LID - 10.1038/s41419-018-0298-2 [doi]
LID - 290
AB  - Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise 
      in the prevention of acute graft-versus-host disease (GVHD) in allogeneic 
      hematopoietic stem cell transplantation patients. However, strategies are needed 
      to improve tTreg proliferative ability and survival as a means to improve tTreg 
      therapy and reduce the requirement for producing large numbers of Treg cells for 
      adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic 
      components, which is involved in cells death, differentiation, lymphocyte 
      homeostasis, and tTreg function. Studies have shown that mice with tTreg cells 
      that have a disrupted autophagy process have defective tTreg cell generation and 
      function, resulting in autoimmune disease and failed GVHD prevention by 
      adoptively transferred tTreg cells. We found the attenuated autophagy status 
      during ex vivo expansion, which leads us to determine whether tTreg cell survival 
      could be augmented by miR-142-3p, the miRNA which is highly expressed in tTreg 
      cells and potentially targets autophagy-related protein (ATG)-1, ATG16L1. We 
      demonstrate that miR-142-3p downregulates ATG16L1 mRNA and production of ATG16L1, 
      that has been linked to autoimmune diseases. Conversely, miR-142-3p knock-down 
      improved tTreg cell expansion, survival and function in vitro and vivo. In 
      aggregate, these studies provide a new approach that uses miR-142-3p knockdown to 
      increase tTreg cell efficacy by increasing ATG16L1 mRNA and protein and the 
      autophagy process.
FAU - Lu, Yunjie
AU  - Lu Y
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Gao, Ji
AU  - Gao J
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Zhang, Shaopeng
AU  - Zhang S
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Gu, Jian
AU  - Gu J
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Lu, Hao
AU  - Lu H
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Xia, Yongxiang
AU  - Xia Y
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Zhu, Qin
AU  - Zhu Q
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Qian, Xiaofeng
AU  - Qian X
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Zhang, Chuanyong
AU  - Zhang C
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Shen, Hongbing
AU  - Shen H
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China.
FAU - Hippen, Keli L
AU  - Hippen KL
AD  - Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN, 
      55455, USA.
FAU - Blazar, Bruce R
AU  - Blazar BR
AD  - Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN, 
      55455, USA.
FAU - Lu, Ling
AU  - Lu L
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China. 
      lvling@njmu.edu.cn.
FAU - Wang, Xuehao
AU  - Wang X
AD  - Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical 
      University, No. 300 Guangzhou Road, Jiangsu Province, Nanjing, 210029, China. 
      wangxh@njmu.edu.cn.
LA  - eng
GR  - P01 AI056299/AI/NIAID NIH HHS/United States
GR  - P01 CA065493/CA/NCI NIH HHS/United States
GR  - R01 HL118979/HL/NHLBI NIH HHS/United States
GR  - R37 AI034495/AI/NIAID NIH HHS/United States
GR  - R37 HL056067/HL/NHLBI NIH HHS/United States
GR  - R01 HL056067/HL/NHLBI NIH HHS/United States
GR  - P01 CA142106/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180219
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Atg16l1 protein, mouse)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn142 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Autophagy-Related Proteins
MH  - Carrier Proteins/genetics/*immunology
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - MicroRNAs/genetics/*immunology/metabolism
MH  - T-Lymphocytes, Regulatory/*cytology/immunology
MH  - Thymus Gland/*cytology/immunology
PMC - PMC5833855
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/02/21 06:00
MHDA- 2019/10/23 06:00
PMCR- 2018/02/19
CRDT- 2018/02/21 06:00
PHST- 2017/11/27 00:00 [received]
PHST- 2018/01/04 00:00 [accepted]
PHST- 2017/12/30 00:00 [revised]
PHST- 2018/02/21 06:00 [entrez]
PHST- 2018/02/21 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/02/19 00:00 [pmc-release]
AID - 10.1038/s41419-018-0298-2 [pii]
AID - 298 [pii]
AID - 10.1038/s41419-018-0298-2 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Feb 19;9(3):290. doi: 10.1038/s41419-018-0298-2.