Monomethyl fumarate prevents alloimmune rejection in mouse heart transplantation by inducing tolerogenic dendritic cells.

Autor: Chen J; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China., Cao Y; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China., Jia O; Nursing Department of Huashan Hospital Affiliated to Fudan University, Shanghai 200031, China., Wang X; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China., Luo Y; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China., Cheuk YC; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China., Zhu T; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China., Zhu D; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.; Department of Urology, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen 361015, China., Zhang Y; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.; Biomedical Research Center, Institute for Clinical Sciences, Zhongshan Hospital, Fudan University, Shanghai 200032, China., Wang J; Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.; Shanghai Key Laboratory of Organ Transplantation, Shanghai 200032, China.
Jazyk: angličtina
Zdroj: Acta biochimica et biophysica Sinica [Acta Biochim Biophys Sin (Shanghai)] 2023 May 16; Vol. 55 (5), pp. 866-877.
DOI: 10.3724/abbs.2023088
Abstrakt: 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.
Databáze: MEDLINE
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