详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Downregulation of N6-Methyladenosine (m6A) Methylation of Sema4D mRNA Contributes to Treg Dysfunction and Allograft Rejection

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]Department of Gastrointestinal Surgery, Sichuan Provincial People's Hospital.University of Electronic Science and Technology of China, Chengdu, SichuanProvince, China [2]Department of Oncology, Medical Research Center, Affiliated Hospital ofSouthwest Jiao Tong University, The Third People's Hospital ofChengdu, Chengdu.Sichuan Province, China [3]Organ Transplantation Center, Sichuan Academy of Medical Sciences & SichuanProvincial People's Hospital, Chengdu, Sichuan Province, ChinaClinical Immunology Translational Medicine Key Laboratory of Sichuan Province [4]Chengdu, Sichuan Province, China Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center [5]Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital.University of Electronic Science and Technology of China, Chengdu, SichuanProvince, China [6]Institute of Neurology, Sichuan Academy of Medical Sciences & SichuanProvincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China [7]The Seventh People's Hospital of Chengdu affiliated Cancer Hospital of ChengduMedical College, Chengdu, Sichuan Province, China

出处：

DOI：

ISSN：

关键词： Transplant rejection METTL14-mediated m6A Treg Sema4D

摘要：

Regulatory T cells (Tregs) has been shown to be involved in the induction of transplantation tolerance in numerous models. Our previous work demonstrated that METTL14 loss impaired Treg function and hindered the establishment of transplantation tolerance. However, the underlying mechanisms remain unclear. In this study, we found that METTL14 knockdown in Tregs significantly impaired their regulatory function, leading to poor allograft function and accelerated transplant rejection. Through MeRIP and mRNA sequencing approaches, we discovered that METTL14 deficiency fostered the expression of Sema4D mRNA, a key semaphorin family member with immunoregulatory activity. Methylation of target adenosines reduced Sema4D mRNA degradation, a process mediated by the METTL14-YTHDF2 axis. Inhibition of Sema4D suppressed its interaction with its receptor, thereby preserving Treg immunoregulation capability and prolonging allograft survival through the PAK-STAT5 signaling pathway. Importantly, Sema4D expression in kidney transplant biopsies were negatively correlated with renal allograft survival. In summary, our findings suggest that METTL14 deficiency in Tregs leads to transplant rejection and reveal for the first time that Sema4D may serve as a potential therapeutic target to enhance Treg function in transplantation.Copyright © 2025. Published by Elsevier Inc.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2025]版：

无

最新[2023]版：

大类 | 2 区

医学

小类 | 1 区移植 2 区外科

第一作者：

第一作者机构： [1]Department of Gastrointestinal Surgery, Sichuan Provincial People's Hospital.University of Electronic Science and Technology of China, Chengdu, SichuanProvince, China [2]Department of Oncology, Medical Research Center, Affiliated Hospital ofSouthwest Jiao Tong University, The Third People's Hospital ofChengdu, Chengdu.Sichuan Province, China

共同第一作者：

通讯作者：

通讯机构： [1]Department of Gastrointestinal Surgery, Sichuan Provincial People's Hospital.University of Electronic Science and Technology of China, Chengdu, SichuanProvince, China [4]Chengdu, Sichuan Province, China Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center

推荐引用方式(GB/T 7714)：

APA：

MLA：

相关文献

[1]Transbronchial Cryobiopsy Versus Transbronchial Forceps Biopsy for Acute Cellular Rejection Detection in Lung Transplantation: A Meta-Analysis [2]Irradiated esophageal squamous cell carcinoma cells induced the increase of Treg by TGF-beta. [3]Mechanism of Increased Treg Frequency Induced by Irradiated Esophageal Squamous Cell Carcinoma [4]Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner. [5]Correlation between peripheral blood CD4 [6]Irradiated esophageal squamous cell carcinoma cells induced the increase of Treg by TGF-beta [7]Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review [8]APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma [9]The Function of Ubiquitination in T-Cell Development [10]Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthritis.