The novel role of beta3 integrin in regulating alloimmunity

β3整合素在调节同种免疫中的新作用

基本信息

  • 批准号:
    10573306
  • 负责人:
  • 金额:
    $ 76.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-02-14 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

Abstract Heart transplantation is the optimal therapy for patients with irreversible, end-stage heart disease. However, a several challenges remain to improve allograft and recipient survival. Immunosuppressive agents used to prevent rejection have improved, but they still cannot consistently eliminate acute and chronic rejection, and they are implicated in the pathogenesis of organ failure. New insights into how innate and adaptive immunity contribute to rejection, identification of new therapeutic targets, and novel approaches to promote immune tolerance are major unmet needs in transplantation. Early innate inflammatory responses in the organs (e.g., due to ischemia-reperfusion injuries) enhance acute and chronic heart allograft rejection. Integrins are heterodimeric cell surface receptors involved in immune cell trafficking and signaling; therefore, they are attractive targets to inhibit inflammation, including transplant rejection. The main goal of this project is to elucidate the novel role of β3 integrin in regulating alloimmune responses via control of platelet- and T cell- mediated immunity. Our ultimate objective is to develop new anti-β3 integrin-based strategies to promote engraftment. Our data indicate that β3 integrin-/- mice (β3-/-) show significantly prolonged heart allograft survival in comparison to wild-type (WT) mice, a finding that is associated with reduced CD8+ T cell infiltration into the grafts. We also show that β3 is expressed by activated CD8+ T cells, and that the trafficking of T cells from β3-/- mice is impaired. Notably, targeting β3 integrin also substantially reduces lesions typical of chronic rejection. The β3 subunit is shared by the two integrin molecules, αVβ3 and αIIbβ3, which are expressed by T cells and platelets, respectively. Based on extensive preliminary data, our specific hypothesis is that β3 on both cell types contributes to rejection. In this proposal, we aim to define the relative roles of β3 integrins expressed on platelets (in early promotion of inflammatory responses) and T cells (in enhancement of alloimmunity) in mediating allograft rejection. Furthermore, our targeted delivery method of therapeutics usingnanoparticles (NPs) has emerged as a promising method that increases efficacy and reduces side effects. Here, we have developed first- in-class NPs for targeted delivery of cyclic RGD tripeptides (cRGD) to suppress β3 integrin- mediated recruitment of platelets and T cells for early reduction of chronic rejection, using a murine model of heart transplantation. In this proposal, we present three main aims to determine the roles of αIIbβ3 on platelets (Aim 1) and T cell- expressed β3 (Aim 2) in regulating alloimmunity. In Aim 3, we will perfuse organs prior to transplantation with NPs carrying cRGD to promote graft acceptance.
摘要

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 }}

Reza Abdi其他文献

Reza Abdi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('Reza Abdi', 18)}}的其他基金

Targeted immune therapies in heart transplantation
心脏移植中的靶向免疫治疗
  • 批准号:
    10573846
  • 财政年份:
    2023
  • 资助金额:
    $ 76.13万
  • 项目类别:
The novel role of beta3 integrin in regulating alloimmunity
β3整合素在调节同种免疫中的新作用
  • 批准号:
    10467425
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
New way in delivering immunomodulatory drugs in T1D
在 T1D 中提供免疫调节药物的新方法
  • 批准号:
    10576373
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
New way in delivering immunomodulatory drugs in T1D
在 T1D 中提供免疫调节药物的新方法
  • 批准号:
    10457732
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
Lymph Node Delivery in Transplantation
移植中的淋巴结输送
  • 批准号:
    10650172
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
IRI, innate immunity and transplant rejection
IRI、先天免疫和移植排斥
  • 批准号:
    10576902
  • 财政年份:
    2021
  • 资助金额:
    $ 76.13万
  • 项目类别:
IRI, innate immunity and transplant rejection
IRI、先天免疫和移植排斥
  • 批准号:
    10371989
  • 财政年份:
    2021
  • 资助金额:
    $ 76.13万
  • 项目类别:
Lymph nodes at the crossroads of allo immunity and regulation
淋巴结处于同种异体免疫和调节的十字路口
  • 批准号:
    10662304
  • 财政年份:
    2020
  • 资助金额:
    $ 76.13万
  • 项目类别:
HVEM pathway regulating FRC function and transplant tolerance
HVEM 通路调节 FRC 功能和移植耐受
  • 批准号:
    10662313
  • 财政年份:
    2020
  • 资助金额:
    $ 76.13万
  • 项目类别:
Admin Core
管理核心
  • 批准号:
    10224022
  • 财政年份:
    2020
  • 资助金额:
    $ 76.13万
  • 项目类别:

相似海外基金

How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
  • 批准号:
    BB/Y004841/1
  • 财政年份:
    2024
  • 资助金额:
    $ 76.13万
  • 项目类别:
    Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
  • 批准号:
    BB/Y001427/1
  • 财政年份:
    2024
  • 资助金额:
    $ 76.13万
  • 项目类别:
    Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
  • 批准号:
    BB/Y005414/1
  • 财政年份:
    2024
  • 资助金额:
    $ 76.13万
  • 项目类别:
    Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
  • 批准号:
    10669829
  • 财政年份:
    2023
  • 资助金额:
    $ 76.13万
  • 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
  • 批准号:
    10587090
  • 财政年份:
    2023
  • 资助金额:
    $ 76.13万
  • 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
  • 批准号:
    10821599
  • 财政年份:
    2023
  • 资助金额:
    $ 76.13万
  • 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
  • 批准号:
    10841832
  • 财政年份:
    2023
  • 资助金额:
    $ 76.13万
  • 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
  • 批准号:
    10532480
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
  • 批准号:
    10741261
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
  • 批准号:
    10674894
  • 财政年份:
    2022
  • 资助金额:
    $ 76.13万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了