Deconstructing B cell transplantation tolerance

解构B细胞移植耐受性

基本信息

  • 批准号:
    10216969
  • 负责人:
  • 金额:
    $ 54.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Summary/Abstract Transplantation tolerance, a state in which immunosuppression can be stopped while grafts remain functional, is a major goal in clinical transplantation field as it promises to reduce side effects, costs and non-adherence consequences associated with the current need for life-long immunosuppression. Tolerance can be spontaneously achieved in rare recipients of kidney allografts and more frequently in liver transplant recipients. In some cases tolerance is stable, while in others the allografts eventually fail. Emerging data have led us to hypothesize that robust peripherally induced transplantation tolerance depends on multiple redundant cell- intrinsic and -extrinsic mechanisms to control alloreactive T and B cells. This proposal focuses of defining the mechanisms that control alloreactive B cells. This focus is based on considerable experimental and clinical data that donor-specific antibody (DSA) is an independent barrier to long-term graft acceptance, and clinical observation that the development of antibodies in tolerant patients leads ultimately to allograft rejection. Over the past few years, my laboratory has focused on tracing the fate of endogenous alloreactive B cells in transplantation rejection and tolerance. Here, we propose to build on our exciting preliminary observations made in a mouse model of cardiac allograft tolerance that donor-specific B cells are not completely deleted but acquire a cell-autonomous dysfunctional state that prevents their differentiation into antibody-secreting cells and that is resistant to T cell help. However, these tolerant cells are not completely inert and, remarkably, are able to suppress naïve B cells in a donor-specific manner. We propose to define the: Aim 1. in vivo cellular requirements for donor-reactive B cells to become intrinsically tolerant; Aim 2. mechanisms maintaining donor- specific B cell-intrinsic tolerance and preventing their development into antibody-secreting cells; Aim 3. Mechanisms and consequences of tolerant B cell-mediated suppression. We anticipate that the completion of these studies will provide insights into novel mechanisms that result in and maintain B cell tolerance, biomarkers that distinguish tolerant B cells from naïve or effector/memory B cells, and potential therapeutic targets for controlling allograft-specific antibody responses in transplant recipients.
总结/摘要 移植耐受,即免疫抑制可以停止而移植物仍保持功能的状态, 是临床移植领域的主要目标,因为它承诺减少副作用、成本和不依从性 与目前需要终身免疫抑制相关的后果。耐受可 在罕见的肾移植受者中自发实现,在肝移植受者中更常见。 在某些情况下,耐受性是稳定的,而在另一些情况下,同种异体移植物最终失败。新的数据让我们 假设强大外周诱导的移植耐受依赖于多个冗余细胞, 控制同种异体反应性T和B细胞的内在和外在机制。该提案的重点是界定 控制同种异体反应性B细胞的机制。这一重点是基于大量的实验和临床 数据表明,供体特异性抗体(DSA)是长期移植物接受的独立障碍, 观察到耐受患者体内抗体的产生最终导致同种异体移植物排斥。超过 在过去的几年里,我的实验室一直致力于追踪内源性同种异体反应性B细胞在 移植排斥和耐受。在这里,我们建议在我们令人兴奋的初步观察的基础上, 在心脏同种异体移植耐受的小鼠模型中制备,供体特异性B细胞没有完全缺失, 获得细胞自主功能障碍状态,阻止其分化为抗体分泌细胞 它对T细胞的帮助有抵抗力。然而,这些耐受细胞并不是完全惰性的,并且值得注意的是, 能够以供体特异性方式抑制幼稚B细胞。我们建议定义:目标1。体内细胞 供体反应性B细胞成为固有耐受性的要求;目标2.维持捐助国- 特异性B细胞内在耐受性并防止其发育为抗体分泌细胞;目的3. 耐受性B细胞介导的抑制的机制和后果。我们预计, 这些研究将提供对导致和维持B细胞耐受性的新机制的深入了解, 区分耐受性B细胞与幼稚或效应/记忆B细胞的生物标志物,以及潜在的治疗 用于控制移植受体中同种异体移植物特异性抗体应答的靶点。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Anita S Chong其他文献

Anita S Chong的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Anita S Chong', 18)}}的其他基金

Intrarenal B cells in acute kidney allograft rejection
肾内 B 细胞在急性同种肾移植排斥反应中的作用
  • 批准号:
    10543172
  • 财政年份:
    2020
  • 资助金额:
    $ 54.93万
  • 项目类别:
Intrarenal B cells in acute kidney allograft rejection
肾内 B 细胞在急性同种肾移植排斥反应中的作用
  • 批准号:
    9980656
  • 财政年份:
    2020
  • 资助金额:
    $ 54.93万
  • 项目类别:
Intrarenal B cells in acute kidney allograft rejection
肾内 B 细胞在急性同种肾移植排斥反应中的作用
  • 批准号:
    10329990
  • 财政年份:
    2020
  • 资助金额:
    $ 54.93万
  • 项目类别:
Deconstructing B cell transplantation tolerance
解构B细胞移植耐受性
  • 批准号:
    10455472
  • 财政年份:
    2019
  • 资助金额:
    $ 54.93万
  • 项目类别:
Supramolecular nanofiber vaccines
超分子纳米纤维疫苗
  • 批准号:
    8911035
  • 财政年份:
    2015
  • 资助金额:
    $ 54.93万
  • 项目类别:
Supramolecular nanofiber vaccines
超分子纳米纤维疫苗
  • 批准号:
    9402045
  • 财政年份:
    2015
  • 资助金额:
    $ 54.93万
  • 项目类别:
Supramolecular nanofiber vaccines
超分子纳米纤维疫苗
  • 批准号:
    9217567
  • 财政年份:
    2015
  • 资助金额:
    $ 54.93万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8512663
  • 财政年份:
    2013
  • 资助金额:
    $ 54.93万
  • 项目类别:
Impact of Infections on the Stability of Established Tolerance
感染对既定耐受稳定性的影响
  • 批准号:
    8512661
  • 财政年份:
    2013
  • 资助金额:
    $ 54.93万
  • 项目类别:
Infections and The Stability of Transplantation Tolerance
感染和移植耐受的稳定性
  • 批准号:
    8512659
  • 财政年份:
    2012
  • 资助金额:
    $ 54.93万
  • 项目类别:

相似海外基金

Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
  • 批准号:
    23H01982
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
  • 批准号:
    23KJ0116
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
  • 批准号:
    10598276
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
  • 批准号:
    10682794
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233343
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
  • 批准号:
    2233342
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
  • 批准号:
    479363
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
  • 批准号:
    10681989
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
  • 批准号:
    2237240
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
  • 批准号:
    2305592
  • 财政年份:
    2023
  • 资助金额:
    $ 54.93万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了