BCR-钙信号通路在间质干细胞诱导调节性B细胞治疗cGVHD中的作用机制研究
结题报告
批准号:
81970109
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
陈小湧
依托单位:
学科分类:
造血、造血调控与造血微环境
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
陈小湧
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中文摘要
慢性移植物抗宿主病(cGVHD)是造血干细胞移植后期主要并发症和死亡原因,申请人前期研究发现间质干细胞(MSC)治疗cGVHD安全有效,且cGVHD症状改善与调节性B细胞(Breg)密切相关,进一步研究显示MSC能增加Breg的数量与IL-10合成,并伴随BCR信号通路激活和钙内流的增加,抑制BCR/钙信号通路显著降低MSC对Breg的调节作用,提示BCR-钙信号通路可能在MSC调控Breg中扮演重要角色。据此,本研究拟利用体内外模型系统探究Breg亚群在MSC治疗cGVHD中的变化规律,揭示BCR信号通路Syk、Btk等激酶与钙信号通路在MSC调控Breg数量与功能中的作用模式;利用转录组测序等技术发掘并验证THBS1、ICAM1等分子在MSC调控BCR-钙信号诱导Breg中的作用机制。上述研究将有助于揭示MSC调控Breg的新机制,阐明MSC治疗cGVHD的机理,推动MSC的临床转化。
英文摘要
Chronic graft-versus-host disease (cGVHD) is a major complication of hematopoietic stem cell transplantation, and the major cause for death in the later stages. Our previous study found that mesenchymal stem cells (MSC) therapy is a safe and effective for treating cGVHD, and the improvement of cGVHD symptoms is closely related to regulatory B cells (Breg). Furthermore, we found that MSC could increase the number of Breg and their IL-10 synthesis, accompanied by BCR signaling pathway activation and calcium influx increase. Blocked the BCR or calcium signaling pathway significantly reduced the MSC-mediated induction of Breg. These suggest that BCR-calcium signaling pathway may play an important role in MSC-mediated induction of Breg. Thus, this study will explore the changes of Breg subpopulation in cGVHD patients that receiving MSC infusions. Using the cell and animal models to reveal the role of Syk, Btk (the key kinase of BCR signaling pathways) and calcium pathways in the MSC-mediated regulation of the number and function of Breg. Using transcriptome sequencing technology and other techniques to explore and verify the roles of THBS1, ICAM1 and other molecules in regulating BCR-calcium signaling pathway for MSC-mediated induction of Breg. These studies will help to reveal the new mechanism for MSC-mediated induction of Breg, and to elucidate the therapeutic mechanisms of MSC improve cGVHD, as well as to promote the clinical translation of MSC.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.3389/fimmu.2020.01843
发表时间:2020
期刊:Frontiers in Immunology
影响因子:7.3
作者:Liu Jialing;Liu Qiuli;Chen Xiaoyong
通讯作者:Chen Xiaoyong
DOI:10.3969/j.issn.1674-7445.2023.03.002
发表时间:2023
期刊:器官移植
影响因子:--
作者:鲍颖颖;陈小湧
通讯作者:陈小湧
Mesenchymal Stromal Cells Rapidly Suppress TCR Signaling-Mediated Cytokine Transcription in Activated T Cells Through the ICAM-1/CD43 Interaction.
间充质基质细胞通过 ICAM-1/CD43 相互作用快速抑制活化 T 细胞中 TCR 信号介导的细胞因子转录。
DOI:10.3389/fimmu.2021.609544
发表时间:2021
期刊:Frontiers in immunology
影响因子:7.3
作者:Zheng S;Huang K;Xia W;Shi J;Liu Q;Zhang X;Li G;Chen J;Wang T;Chen X;Xiang AP
通讯作者:Xiang AP
DOI:10.1038/s41392-022-01124-6
发表时间:2022-09-05
期刊:SIGNAL TRANSDUCTION AND TARGETED THERAPY
影响因子:39.3
作者:Zhang, Xiaoran;Wei, Xuxia;Deng, Yiwen;Yuan, Xiaofeng;Shi, Jiahao;Huang, Weijun;Huang, Jing;Chen, Xiaoyong;Zheng, Shuwei;Chen, Jieying;Chen, Keyu;Xu, Ruiming;Wang, Hongmiao;Li, Weiqiang;Li, Shiyue;Yi, Huimin;Xiang, Andy Peng
通讯作者:Xiang, Andy Peng
Efficacy and Safety of Bone Marrow-Derived Mesenchymal Stem Cells for Chronic Antibody-Mediated Rejection After Kidney Transplantation- A Single-Arm, Two-Dosing-Regimen, Phase I/II Study.
骨髓间充质干细胞治疗肾移植后慢性抗体介导的排斥反应的功效和安全性——单臂、两次给药方案、I/II 期研究
DOI:10.3389/fimmu.2021.662441
发表时间:2021
期刊:Frontiers in immunology
影响因子:7.3
作者:Wei Y;Chen X;Zhang H;Su Q;Peng Y;Fu Q;Li J;Gao Y;Li X;Yang S;Ye Q;Huang H;Deng R;Li G;Xu B;Wu C;Wang J;Zhang X;Su X;Liu L;Xiang AP;Wang C
通讯作者:Wang C
CD21low/-CD23-B细胞亚群在间质干细胞治疗慢性移植物抗宿主病中的作用机制研究
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    52万元
  • 批准年份:
    2022
  • 负责人:
    陈小湧
  • 依托单位:
间质干细胞对CD23+CD43+调节性B细胞的调控作用及机制研究
  • 批准号:
    81600102
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    18.0万元
  • 批准年份:
    2016
  • 负责人:
    陈小湧
  • 依托单位:
国内基金
海外基金