PMID- 33597869
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210219
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Regulating T Cell Population Alleviates SLE by Inhibiting mTORC1/C2 in MRL/lpr 
      Mice.
PG  - 579298
LID - 10.3389/fphar.2020.579298 [doi]
LID - 579298
AB  - It's well known that the mammalian target of rapamycin (mTOR) exerts a critical 
      role in the regulator of immune cells and is associated with T cells dysfunction 
      in patients with systemic lupus erythematosus (SLE). Antigen-induced T-cell 
      proliferation via mTORC1 suppressed by Rapamycin has been used to improve SLE 
      primarily. Previously it has showed that INK128, a highly potent, specific orally 
      inhibitor of mTORC1 and mTORC2, significantly attenuates SLE in pristine-induced 
      lupus mice. Herein we compared the cure effects of INK128 and rapamycin on lupus 
      mice. We treated MRL/lpr mice with INK128 or rapamycin at 12 weeks-age. The 
      effect of the two inhibitors on the lupus mice was determined by 
      immunohistochemistry. The effect of the two inhibitors on T cell populations was 
      investigated by flow cytometry. The mTOR signaling was measured by Western Blot. 
      INK128 remarkably alleviated SLE by reducing splenomegaly, renal inflammation and 
      damage, and resuming T-cell dysfunction. The more effective of INK128 on SLE than 
      rapamycin. INK128 effectively suppressed mTORC1 and mTORC2 activity in T cells, 
      but rapamycin just suppressed mTORC1 activity. Thus, our results show that INK128 
      is can effectively alleviate SLE and be used as one of the potential clinical 
      therapeutic candidates for SLE.
CI  - Copyright (c) 2021 Zhang, Wang, Shi, Pan, Ji and Li.
FAU - Zhang, Dongya
AU  - Zhang D
AD  - Key Laboratory of Inflammation and Immunoregulation, School of Medical and 
      Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 
      China.
FAU - Wang, Meiling
AU  - Wang M
AD  - Key Laboratory of Inflammation and Immunoregulation, School of Medical and 
      Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 
      China.
FAU - Shi, Guoping
AU  - Shi G
AD  - Department of Clinical Laboratory, Jiangsu Province Hospital of Traditional 
      Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, 
      Nanjing, China.
FAU - Pan, Peng
AU  - Pan P
AD  - Department of Anesthesiology, Kunshan Hospital of Traditional Chinese Medicine, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, China.
FAU - Ji, Jianjian
AU  - Ji J
AD  - Key Laboratory of Inflammation and Immunoregulation, School of Medical and 
      Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 
      China.
AD  - Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Li, Pengfei
AU  - Li P
AD  - Department of Clinical Laboratory, Jiangsu Province Hospital of Traditional 
      Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, 
      Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20210114
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7883674
OTO - NOTNLM
OT  - INK128
OT  - SLE
OT  - T cell populations
OT  - mTOR
OT  - rapamycin
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/19 06:00
MHDA- 2021/02/19 06:01
PMCR- 2021/01/14
CRDT- 2021/02/18 06:10
PHST- 2020/07/17 00:00 [received]
PHST- 2020/09/24 00:00 [accepted]
PHST- 2021/02/18 06:10 [entrez]
PHST- 2021/02/19 06:00 [pubmed]
PHST- 2021/02/19 06:01 [medline]
PHST- 2021/01/14 00:00 [pmc-release]
AID - 579298 [pii]
AID - 10.3389/fphar.2020.579298 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Jan 14;11:579298. doi: 10.3389/fphar.2020.579298. 
      eCollection 2020.