PMID- 32566604
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 8
IP  - 9
DP  - 2020 May
TI  - Glucose metabolism pattern of peripheral blood immune cells in myasthenia gravis 
      patients.
PG  - 577
LID - 10.21037/atm-20-918 [doi]
LID - 577
AB  - BACKGROUND: We investigated the correlation between glucose metabolism patterns 
      of different immune cells and the metabolic regulatory signaling pathways in 
      myasthenia gravis (MG) and aimed to identify therapeutic targets for MG. METHODS: 
      We isolated peripheral blood mononuclear cells (PBMCs) and sorted CD19(+)B cells, 
      dendritic cells (DCs), CD4(+) T cells, CD8(+) T cells, CD4(+)CD25(+) regulatory T 
      cells (Tregs), CD4(+)CD25(-)T cells, and T helper (Th) cells such as Th1, Th2, 
      and Th17 cells. Then, we detected the expression levels of PI3K/AKT/mTOR-HIF-1alpha, 
      GLUT1, hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) by 
      RT-PCR, measured the oxygen consumption rate and extracellular acidification rate 
      of ex vivo freshly sorted cells using the Seahorse XF(e)96 Analyzer. In addition, 
      we compared the glycolysis levels using these cells from the same MG patients. By 
      performing in vitro experiments, we measured, the mRNA expression levels of mTOR, 
      HIF-1alpha, B cell activating factor receptor (BAFF-R), GLUT1, HK, PFK, and PK, in 
      addition to ECAR profiles, frequency of CD80 and CD86, and IgG levels from the 
      culture supernatant of B cells (isolated from MG patients) treated with rapamycin 
      and PX-478 (selective mTOR and HIF-1alpha inhibitor, respectively) from. RESULTS: 
      Except PBMCs, Th2 and CD8(+) T cells, the expression levels of the key enzymes 
      involved in glycolysis and HIF-1alpha were significantly higher in B cells, DCs, 
      Tregs, CD4(+)CD25(-)T cells, and Th1 and Th17 cells in MG patients, and the 
      measurement of ECAR and OCR confirmed the metabolic status. In MG patients, B 
      cells and DCs showed significantly higher levels of glycolysis and glycolytic 
      capacity than CD8(+) T cells, CD4(+) T cells and its subsets. In vitro, except 
      IgG levels, the increased glycolysis levels, expression of key glycolytic 
      enzymes, BAFF-R and frequency of CD80 and CD86 of B cells, could be inhibited by 
      rapamycin and PX-478. CONCLUSIONS: Different subtypes of immune cells in MG 
      exhibit different glucose metabolism patterns. The mTOR-HIF-1alpha signaling pathway 
      might be the immunometabolism reprogramming checkpoint of glycolysis-dependent 
      activated B cells in MG.
CI  - 2020 Annals of Translational Medicine. All rights reserved.
FAU - Li, Zhibin
AU  - Li Z
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Peng, Yuyao
AU  - Peng Y
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Zhou, Ran
AU  - Zhou R
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Chen, Di
AU  - Chen D
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Jin, Wanlin
AU  - Jin W
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Xu, Qiu
AU  - Xu Q
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Xu, Liqun
AU  - Xu L
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Luo, Zhaohui
AU  - Luo Z
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
FAU - Yang, Huan
AU  - Yang H
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha 
      410008, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC7290526
OTO - NOTNLM
OT  - HIF-1alpha
OT  - Myasthenia gravis (MG)
OT  - glucose metabolism
OT  - immune cells
OT  - mTOR
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/atm-20-918). The authors have no 
      conflicts of interest to declare.
EDAT- 2020/06/23 06:00
MHDA- 2020/06/23 06:01
PMCR- 2020/05/01
CRDT- 2020/06/23 06:00
PHST- 2020/06/23 06:00 [entrez]
PHST- 2020/06/23 06:00 [pubmed]
PHST- 2020/06/23 06:01 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - atm-08-09-577 [pii]
AID - 10.21037/atm-20-918 [doi]
PST - ppublish
SO  - Ann Transl Med. 2020 May;8(9):577. doi: 10.21037/atm-20-918.