PMID- 37184280
OWN - NLM
STAT- MEDLINE
DCOM- 20230621
LR  - 20230701
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Print)
IS  - 1672-9145 (Linking)
VI  - 55
IP  - 5
DP  - 2023 May 16
TI  - Monomethyl fumarate prevents alloimmune rejection in mouse heart transplantation 
      by inducing tolerogenic dendritic cells.
PG  - 866-877
LID - 10.3724/abbs.2023088 [doi]
AB  - Dendritic cells (DCs) are important targets for eliciting allograft rejection 
      after transplantation. Previous studies have demonstrated that metabolic 
      reprogramming of DCs can transform their immune functions and induce their 
      differentiation into tolerogenic DCs. In this study, we aim to investigate the 
      protective effects and mechanisms of monomethyl fumarate (MMF), a bioactive 
      metabolite of fumaric acid esters, in a mouse model of allogeneic heart 
      transplantation. Bone marrow-derived DCs are harvested and treated with MMF to 
      determine the impact of MMF on the phenotype and immunosuppressive function of 
      DCs by flow cytometry and T-cell proliferation assays. RNA sequencing and 
      Seahorse analyses are performed for mature DCs and MMF-treated DCs (MMF-DCs) to 
      investigate the underlying mechanism. Our results show that MMF prolongs the 
      survival time of heart grafts and inhibits the activation of DCs in vivo. MMF-DCs 
      exhibit a tolerogenic phenotype and function in vitro. RNA sequencing and 
      Seahorse analyses reveal that MMF activates the Nrf2 pathway and mediates 
      metabolic reprogramming. Additionally, MMF-DC infusion prolongs cardiac allograft 
      survival, induces regulatory T cells, and inhibits T-cell activation. MMF 
      prevents allograft rejection in mouse heart transplantation by inducing 
      tolerogenic DCs.
FAU - Chen, Juntao
AU  - Chen J
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
FAU - Cao, Yirui
AU  - Cao Y
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
FAU - Jia, Ouyang
AU  - Jia O
AD  - Nursing Department of Huashan Hospital Affiliated to Fudan University, Shanghai 
      200031, China.
FAU - Wang, Xuanchuan
AU  - Wang X
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
FAU - Luo, Yongsheng
AU  - Luo Y
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
FAU - Cheuk, Yin Celeste
AU  - Cheuk YC
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
FAU - Zhu, Tongyu
AU  - Zhu T
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
FAU - Zhu, Dong
AU  - Zhu D
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
AD  - Department of Urology, Zhongshan Hospital, Fudan University (Xiamen Branch), 
      Xiamen 361015, China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
AD  - Biomedical Research Center, Institute for Clinical Sciences, Zhongshan Hospital, 
      Fudan University, Shanghai 200032, China.
FAU - Wang, Jina
AU  - Wang J
AD  - Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, 
      China.
AD  - Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 45IUB1PX8R (monomethyl fumarate)
RN  - 0 (Fumarates)
RN  - 0 (Tolerogen)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Heart Transplantation
MH  - T-Lymphocytes, Regulatory
MH  - Fumarates/metabolism
MH  - Dendritic Cells
MH  - Immune Tolerance
MH  - Graft Rejection/prevention & control
MH  - Mice, Inbred C57BL
PMC - PMC10281873
OTO - NOTNLM
OT  - Nrf2
OT  - dendritic cell
OT  - heart transplantation
OT  - immune tolerance
OT  - metabolic reprogramming
OT  - monomethyl fumarate
COIS- The authors declare that they have no conflict of interest.
EDAT- 2023/05/15 13:06
MHDA- 2023/06/21 06:42
PMCR- 2023/05/16
CRDT- 2023/05/15 09:13
PHST- 2023/06/21 06:42 [medline]
PHST- 2023/05/15 13:06 [pubmed]
PHST- 2023/05/15 09:13 [entrez]
PHST- 2023/05/16 00:00 [pmc-release]
AID - 10.3724/abbs.2023088 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2023 May 16;55(5):866-877. doi: 
      10.3724/abbs.2023088.