PMID- 30801921
OWN - NLM
STAT- MEDLINE
DCOM- 20200714
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 19
IP  - 6
DP  - 2019 Jun
TI  - The "other" mTOR complex: New insights into mTORC2 immunobiology and their 
      implications.
PG  - 1614-1621
LID - 10.1111/ajt.15320 [doi]
AB  - A central role of the mechanistic target of rapamycin (mTOR) in regulation of 
      fundamental cell processes is well recognized. mTOR functions in two distinct 
      complexes: rapamycin-sensitive mTOR complex (C) 1 and rapamycin-insensitive 
      mTORC2. While the role of mTORC1 in shaping immune responses, including 
      transplant rejection, and the influence of its antagonism in promoting allograft 
      tolerance have been studied extensively using rapamycin, lack of selective small 
      molecule inhibitors has limited understanding of mTORC2 biology. Within the past 
      few years, however, intracellular localization of mTORC2, its contribution to 
      mitochondrial fitness, cell metabolism, cytoskeletal modeling and cell migration, 
      and its role in differentiation and function of immune cells have been described. 
      Studies in mTORC2 knockdown/knockout mouse models and a new class of dual 
      mTORC1/2 inhibitors, have shed light on the immune regulatory functions of 
      mTORC2. These include regulation of antigen-presenting cell, NK cell, T cell 
      subset, and B cell differentiation and function. mTORC2 has been implicated in 
      regulation of ischemia/reperfusion injury and graft rejection. Potential 
      therapeutic benefits of antagonizing mTORC2 to inhibit chronic rejection have 
      also been described, while selective in vivo targeting strategies using 
      nanotechnology have been developed. We briefly review and discuss these 
      developments and their implications.
CI  - (c) 2019 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Dai, Helong
AU  - Dai H
AD  - Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh 
      School of Medicine, Pittsburgh, Pennsylvania.
AD  - Department of Urological Organ Transplantation, The Second Xiangya Hospital of 
      Central South University, Changsha, Hunan, China.
FAU - Thomson, Angus W
AU  - Thomson AW
AD  - Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh 
      School of Medicine, Pittsburgh, Pennsylvania.
AD  - Department of Immunology, University of Pittsburgh School of Medicine, 
      Pittsburgh, Pennsylvania.
LA  - eng
GR  - R21 AI137799/AI/NIAID NIH HHS/United States
GR  - 81800664/National Natural Science Foundation of China/International
GR  - U19 AI131453/AI/NIAID NIH HHS/United States
GR  - U01 AI136779/AI/NIAID NIH HHS/United States
GR  - R01 AI118777/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190319
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/immunology
MH  - Humans
MH  - Immunity, Innate
MH  - Mechanistic Target of Rapamycin Complex 1/immunology
MH  - Mechanistic Target of Rapamycin Complex 2/antagonists & 
      inhibitors/genetics/*immunology
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Models, Immunological
MH  - Reperfusion Injury/immunology
MH  - T-Lymphocyte Subsets/immunology
MH  - Transplantation Immunology
PMC - PMC6538441
MID - NIHMS1013742
OTO - NOTNLM
OT  - basic (laboratory) research/science
OT  - cellular biology
OT  - immunobiology
OT  - immunosuppressant - mechanistic target of rapamycin (mTOR)
OT  - innate immunity
OT  - lymphocyte biology
OT  - molecular biology
OT  - tissue injury and repair
OT  - translational research/science
COIS- DISCLOSURE The authors of this manuscript have no conflicts of interest to 
      disclose as described by the American Journal of Transplantation.
EDAT- 2019/02/26 06:00
MHDA- 2020/07/15 06:00
PMCR- 2020/06/01
CRDT- 2019/02/26 06:00
PHST- 2019/01/16 00:00 [received]
PHST- 2019/02/10 00:00 [revised]
PHST- 2019/02/15 00:00 [accepted]
PHST- 2019/02/26 06:00 [pubmed]
PHST- 2020/07/15 06:00 [medline]
PHST- 2019/02/26 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - S1600-6135(22)09106-7 [pii]
AID - 10.1111/ajt.15320 [doi]
PST - ppublish
SO  - Am J Transplant. 2019 Jun;19(6):1614-1621. doi: 10.1111/ajt.15320. Epub 2019 Mar 
      19.