T cell homing to the kidney contributes to salt retention and blood pressure regulation

T 细胞归巢至肾脏有助于盐潴留和血压调节

基本信息

  • 批准号:
    10608091
  • 负责人:
  • 金额:
    $ 38万
  • 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:
    2019-04-01 至 2024-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY / ABSTRACT The kidneys are important regulators of blood pressure. They regulate circulatory volume by controlling sodium and water balance, thus maintaining extracellular fluid volume homeostasis. It is well established that the pathogenesis of salt-sensitive hypertension is caused by impaired sodium handling in the kidneys, but the critical factors leading to renal sodium retention remain unidentified. An important role for T cells in hypertension has been proposed in the past decade. However, no related feasible treatment options have been proposed, because the mechanisms underlying this role for T cells have not been elucidated. We recently identified a novel role for kidney-infiltrated CD8+ T cells (CD8Ts) in enhancing salt retention; renal infiltrated CD8Ts interact with distal convoluted tubule cells (DCTs), stimulating the sodium-chloride co- transporter (NCC) in the DCTs, resulting in elevation of blood pressure. These findings led us to hypothesize that the interaction between CD8Ts and renal tubular cells mediates T cell-homing to the kidney, which may represent a kidney defect that contributes to the pathogenesis of salt sensitive hypertension. In the proposed study, we will investigate the critical molecular determinants in the kidney, by which CD8Ts interact with renal tubular cells and determine how this kidney-homing mechanism of CD8Ts contributes to excessive salt retention, leading to high blood pressure. Specifically, Aim 1 will test our hypothesis that cytokines produced from activated CD8Ts prime DCTs to express co-signaling molecule, which initiates the interaction between DCTs and CD8Ts; Aim 2 will identify the adhesion molecules that mediate a putative immunological synapse between these two cell types. Aim 3 will determine the critical role of potassium channel Kir4.1 in CD8T- induced upregulation of NCC and possibly other sodium transporters in the distal nephron, leading to excessive salt retention and consequent elevation of blood pressure. Our preliminary studies have identified key molecules for each Aim. As proof of principle experiments, immunological neutralization or genetic deletion of these molecules in the kidneys of mice prevented stimuli-induced upregulation of NCC in the kidney and consequently lowered blood pressure. Complementary in vivo and in vitro studies are designed in this proposal to accomplish our aims. We will use kidney-specific knockout or knockdown methods in animals to determine the precise roles of key molecules in this study. Accomplishing our aims will elucidate the important molecular mechanisms regarding T cell homing to the kidney, thus impairing salt and volume homeostasis, and affecting blood pressure. We propose that salt-sensitive hypertension is caused, at least in part, by immune disorders in the kidney. Moreover, the key molecules identified in this study may represent novel targets for future immunotherapy against this prevalent health problem.
项目摘要/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 }}

Shengyu Mu其他文献

Shengyu Mu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('Shengyu Mu', 18)}}的其他基金

T cell homing to the kidney contributes to salt retention and blood pressure regulation
T 细胞归巢至肾脏有助于盐潴留和血压调节
  • 批准号:
    10394209
  • 财政年份:
    2019
  • 资助金额:
    $ 38万
  • 项目类别:
T cell homing to the kidney contributes to salt retention and blood pressure regulation
T 细胞归巢至肾脏有助于盐潴留和血压调节
  • 批准号:
    9888420
  • 财政年份:
    2019
  • 资助金额:
    $ 38万
  • 项目类别:

相似海外基金

Time to ATTAC: Adoptive Transfer of T cells Against gp100+ Cells to treat LAM
ATTAC 时间:针对 gp100 细胞的 T 细胞过继转移来治疗 LAM
  • 批准号:
    10682121
  • 财政年份:
    2023
  • 资助金额:
    $ 38万
  • 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
  • 批准号:
    10576370
  • 财政年份:
    2022
  • 资助金额:
    $ 38万
  • 项目类别:
Phase I clinical trial of adoptive transfer of autologous folate receptor-alpha redirected CAR T cells for ovarian cancer
自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
  • 批准号:
    10387023
  • 财政年份:
    2022
  • 资助金额:
    $ 38万
  • 项目类别:
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
  • 批准号:
    10248409
  • 财政年份:
    2019
  • 资助金额:
    $ 38万
  • 项目类别:
A phase I clinical study of adoptive transfer of regulatory T cells (Tregs) and low-dose interleukin-2 (IL-2) for the treatment of chronic graft-versus-host disease (GVHD): gene-marking to inform rational combination therapy
调节性 T 细胞 (Treg) 和低剂量白细胞介素 2 (IL-2) 过继转移治疗慢性移植物抗宿主病 (GVHD) 的 I 期临床研究:基因标记为合理的联合治疗提供信息
  • 批准号:
    nhmrc : GNT1163111
  • 财政年份:
    2019
  • 资助金额:
    $ 38万
  • 项目类别:
    Project Grants
Determining mechanisms of enhanced antitumor efficacy of four-day expanded Th17 cells for adoptive transfer
确定用于过继转移的四天扩增 Th17 细胞增强抗肿瘤功效的机制
  • 批准号:
    10462684
  • 财政年份:
    2019
  • 资助金额:
    $ 38万
  • 项目类别:
Gene edited lymphoid progenitors for adoptive transfer as a treatment of primary immunodeficiency
基因编辑的淋巴祖细胞用于过继转移作为原发性免疫缺陷的治疗
  • 批准号:
    398018062
  • 财政年份:
    2018
  • 资助金额:
    $ 38万
  • 项目类别:
    Research Grants
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
  • 批准号:
    9308643
  • 财政年份:
    2017
  • 资助金额:
    $ 38万
  • 项目类别:
Overcoming immune suppression in cancer by targeting PSGL-1 in T cells used for adoptive transfer
通过靶向用于过继转移的 T 细胞中的 PSGL-1 克服癌症中的免疫抑制
  • 批准号:
    9447149
  • 财政年份:
    2017
  • 资助金额:
    $ 38万
  • 项目类别:
Targeting Cancer miRNAs by Adoptive Transfer of Programmed B Lymphocytes
通过程序化 B 淋巴细胞的过继转移靶向癌症 miRNA
  • 批准号:
    8893915
  • 财政年份:
    2014
  • 资助金额:
    $ 38万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了