PMID- 36166182
OWN - NLM
STAT- MEDLINE
DCOM- 20230327
LR  - 20230410
IS  - 1869-1889 (Electronic)
IS  - 1674-7305 (Linking)
VI  - 66
IP  - 3
DP  - 2023 Mar
TI  - Glucocorticoid and glycolysis inhibitors cooperatively abrogate acute 
      graft-versus-host disease.
PG  - 528-544
LID - 10.1007/s11427-022-2170-2 [doi]
AB  - Although glucorticosteroids (GCs) are the standard first-line therapy for acute 
      graft-versus-host disease (aGvHD), nearly 50% of aGvHD patients have no response 
      to GCs. The role of T cell metabolism in murine aGvHD was recently reported. 
      However, whether GCs and metabolism regulators could cooperatively suppress T 
      cell alloreactivity and ameliorate aGvHD remains to be elucidated. Increased 
      glycolysis, characterized by elevated 
      6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), and higher rates 
      of glucose consumption and lactate production were found in T cells from aGvHD 
      patients. Genetic upregulation of PFKFB3 induced T cell proliferation and 
      differentiation into proinflammatory cells. In a humanized mouse model, 
      PFKFB3-overexpressing or PFKFB3-silenced T cells aggravated or prevented aGvHD, 
      respectively. Importantly, our integrated data from patient samples in vitro, in 
      a humanized xenogeneic murine model of aGvHD and graft-versus-leukaemia (GVL) 
      demonstrate that GCs combined with a glycolysis inhibitor could cooperatively 
      reduce the alloreactivity of T cells and ameliorate aGvHD without loss of GVL 
      effects. Together, the current study indicated that glycolysis is critical for T 
      cell activation and induction of human aGvHD. Therefore, the regulation of 
      glycolysis offers a potential pathogenesis-oriented therapeutic strategy for 
      aGvHD patients. GCs combined with glycolysis inhibitors promises to be a novel 
      first-line combination therapy for aGvHD patients.
CI  - (c) 2022. Science China Press and Springer-Verlag GmbH Germany, part of Springer 
      Nature.
FAU - Wen, Qi
AU  - Wen Q
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Xu, Zheng-Li
AU  - Xu ZL
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Lv, Meng
AU  - Lv M
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Song, Yang
AU  - Song Y
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
AD  - Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary 
      Studies, Peking University, Beijing, 100044, China.
FAU - Lyv, Zhong-Shi
AU  - Lyv ZS
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
AD  - Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary 
      Studies, Peking University, Beijing, 100044, China.
FAU - Xing, Tong
AU  - Xing T
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Xu, Lan-Ping
AU  - Xu LP
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Zhang, Xiao-Hui
AU  - Zhang XH
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
FAU - Huang, Xiao-Jun
AU  - Huang XJ
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China.
AD  - Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary 
      Studies, Peking University, Beijing, 100044, China.
FAU - Kong, Yuan
AU  - Kong Y
AD  - Peking University People's Hospital, Peking University Institute of Hematology, 
      National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory 
      of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of 
      Hematology, Peking University, Beijing, 100044, China. successky@163.com.
LA  - eng
PT  - Journal Article
DEP - 20220922
PL  - China
TA  - Sci China Life Sci
JT  - Science China. Life sciences
JID - 101529880
RN  - 0 (Glucocorticoids)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Glucocorticoids
MH  - Acute Disease
MH  - T-Lymphocytes/metabolism
MH  - *Graft vs Host Disease/drug therapy/etiology
MH  - Glycolysis
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
OTO - NOTNLM
OT  - T cells
OT  - allogeneic haematopoietic stem cell transplantation
OT  - glycolysis
OT  - graft versus host disease
OT  - human
EDAT- 2022/09/28 06:00
MHDA- 2023/03/28 06:00
CRDT- 2022/09/27 12:00
PHST- 2022/05/20 00:00 [received]
PHST- 2022/07/27 00:00 [accepted]
PHST- 2022/09/28 06:00 [pubmed]
PHST- 2023/03/28 06:00 [medline]
PHST- 2022/09/27 12:00 [entrez]
AID - 10.1007/s11427-022-2170-2 [pii]
AID - 10.1007/s11427-022-2170-2 [doi]
PST - ppublish
SO  - Sci China Life Sci. 2023 Mar;66(3):528-544. doi: 10.1007/s11427-022-2170-2. Epub 
      2022 Sep 22.