Regulation of IDDM by Proinflammatory and Th1-cytokines

促炎细胞因子和 Th1 细胞因子对 IDDM 的调节

基本信息

  • 批准号:
    6830703
  • 负责人:
  • 金额:
    $ 39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-12-01 至 2008-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Insulin-dependent diabetes mellitus (IDDM) is characterized by the infiltration of T-lymphocytes into the islets of Langerhans of the pancreas (insulitis), followed by selective destruction of insulin-secreting beta cells leading to overt diabetes. Preliminarily, we observed the important association of IDDM with AIM factor (a secretion molecule we initially identified as an apoptosis inhibitory factor), which are: (1) AIM [-/-] mice backcrossed to non-obese diabetes (NOD) background showed complete prevention of IDDM; (2) AIM is expressed by infiltrating macrophages in the pancreatic islets from the very early stage of the disease; (3) AIM strongly induces TNF-alpha, IL-1 beta, IL-6 and IL-12 in macrophages and dendritic cells (DCs). Based on these, a hypothesis has emerged that AIM may accelerate IDDM by inducing pro-inflammatory- and type I- cytokines in initially infiltrating macrophages and DCs in the islets at the onset stage of the disease. The Specific Aim 1 and 2 are focused on establishing the propriety of the hypothesis by adding back the AIM expression in macrophages in AIM-null NOD mice expecting the disease recurrence (aim 1), and testing the impact of the cytokines downstream of AIM signaling on the disease acceleration by assessing whether the induction of the cytokines in macrophages and DCs via the Tet-inducible transgenic system may overcome the disease prevention in AIM-null NOD mice (aim 2). In addition, our recent result that AIM mediates Toll-signaling to induce the cytokines provoked an idea that the putative AIM-receptor may be a TolI/IL-1 receptor family member. In the Specific Aim 3, we will purify and characterize the AIM-receptor by expression screening of a cDNA library generated from macrophage cells. We also plan to create knockout mice of the AIM-receptor by disrupting the gene in the NOD-derived ES cells, as we generated AIM[-/-]/-NOD by using the cells. Our proposed studies will clarify the precise picture of the IDDM pathogenesis in the context of AIM, in particular, during the early stage of the disease, and thus will contribute to development of a new therapy via suppression of AIM. In addition, identification of AIM-receptor will shed light on the precise molecular machinery of AIM functions, as well as a new aspect of physiological function of the Toll-family.
描述(由申请方提供):胰岛素依赖型糖尿病(IDDM)的特征是T淋巴细胞浸润到胰腺的胰岛(胰岛炎)中,随后选择性破坏分泌胰岛素的β细胞,导致明显的糖尿病。因此,我们观察到了胰岛素依赖型糖尿病与AIM因子的重要联系(一种我们最初鉴定为凋亡抑制因子的分泌分子),它们是:(1)与非肥胖型糖尿病(NOD)背景回交的AIM [-/-]小鼠显示出对IDDM的完全预防;(2)AIM在疾病的非常早期阶段通过胰岛中浸润的巨噬细胞表达;(3)AIM强烈诱导巨噬细胞和树突状细胞(DC)中的TNF-α、IL-1 β、IL-6和IL-12。基于这些,出现了一种假设,即AIM可能通过在疾病发作阶段诱导胰岛中最初浸润的巨噬细胞和DC中的促炎细胞因子和I型细胞因子来加速IDDM。具体目标1和2的重点是通过在预期疾病复发的AIM无效NOD小鼠的巨噬细胞中添加回AIM表达来建立假设的适当性(目标1),以及通过评估巨噬细胞和DC中细胞因子经由泰特-诱导型转基因系统可以克服AIM-null NOD小鼠中的疾病预防(目的2)。此外,我们最近的研究结果表明,AIM介导的Toll信号转导诱导细胞因子引起的想法,推定的AIM受体可能是一个Toll/IL-1受体家族成员。在具体目标3中,我们将通过对巨噬细胞产生的cDNA文库进行表达筛选来纯化和表征AIM受体。我们还计划通过破坏NOD衍生的ES细胞中的基因来创建AIM受体的敲除小鼠,因为我们通过使用细胞产生AIM[-/-]/-NOD。我们提出的研究将阐明在AIM背景下,特别是在疾病的早期阶段,IDDM发病机制的确切情况,因此将有助于通过抑制AIM开发新的治疗方法。此外,AIM受体的鉴定将揭示AIM功能的精确分子机制,以及Toll家族生理功能的一个新方面。

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 }}

TORU MIYAZAKI其他文献

TORU MIYAZAKI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('TORU MIYAZAKI', 18)}}的其他基金

Regulation of IDDM by Proinflammatory and Th1-cytokines
促炎细胞因子和 Th1 细胞因子对 IDDM 的调节
  • 批准号:
    7364546
  • 财政年份:
    2003
  • 资助金额:
    $ 39万
  • 项目类别:
Regulation of IDDM by Proinflammatory and Th1-cytokines
促炎细胞因子和 Th1 细胞因子对 IDDM 的调节
  • 批准号:
    6984786
  • 财政年份:
    2003
  • 资助金额:
    $ 39万
  • 项目类别:
Regulation of IDDM by Proinflammatory and Th1-cytokines
促炎细胞因子和 Th1 细胞因子对 IDDM 的调节
  • 批准号:
    7147442
  • 财政年份:
    2003
  • 资助金额:
    $ 39万
  • 项目类别:
Regulation of IDDM by AIM and Th1-cytokines
AIM 和 Th1 细胞因子对 IDDM 的调节
  • 批准号:
    6609969
  • 财政年份:
    2003
  • 资助金额:
    $ 39万
  • 项目类别:
Regulation of IDDM by Proinflammatory and Th1-cytokines
促炎细胞因子和 Th1 细胞因子对 IDDM 的调节
  • 批准号:
    7210865
  • 财政年份:
    2003
  • 资助金额:
    $ 39万
  • 项目类别:
Regulation of IDDM by Proinflammatory and Th1-cytokines
促炎细胞因子和 Th1 细胞因子对 IDDM 的调节
  • 批准号:
    6731582
  • 财政年份:
    2003
  • 资助金额:
    $ 39万
  • 项目类别:

相似海外基金

AI-PigNet: The AI of social interactions for next gen smart animal breeding
AI-PigNet:下一代智能动物饲养的社交互动人工智能
  • 批准号:
    BB/Y513891/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grant
In vitro embryo production in animal breeding: Enhancing oocyte quality from peri-pubertal donors to promote biosecure and sustainable food production
动物育种中的体外胚胎生产:提高青春期前后捐献者的卵母细胞质量,以促进生物安全和可持续粮食生产
  • 批准号:
    BB/R00708X/1
  • 财政年份:
    2018
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grant
Core 4: Animal Breeding (UAB) and Exposure Core (MRIGLOBAL)
核心 4:动物育种 (UAB) 和暴露核心 (MRIGLOBAL)
  • 批准号:
    10249112
  • 财政年份:
    2018
  • 资助金额:
    $ 39万
  • 项目类别:
In vitro embryo production in animal breeding: Enhancing oocyte quality from peri-pubertal donors to promote biosecure and sustainable food production
动物育种中的体外胚胎生产:提高青春期前后捐献者的卵母细胞质量,以促进生物安全和可持续粮食生产
  • 批准号:
    BB/R007985/1
  • 财政年份:
    2018
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grant
Multicollinearity in the statistical genomics era: Proposals to account for dependencies between molecular covariates with application to animal breeding
统计基因组学时代的多重共线性:解释分子协变量之间依赖性及其在动物育种中的应用的建议
  • 批准号:
    363504750
  • 财政年份:
    2017
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grants
Advanced animal breeding in aquaculture: using genome-wide molecular breeding values for rapid animal improvement in the silver-lipped pearl oyster.
水产养殖中的先进动物育种:利用全基因组分子育种值对银唇珍珠贝进行快速动物改良。
  • 批准号:
    LP140101001
  • 财政年份:
    2015
  • 资助金额:
    $ 39万
  • 项目类别:
    Linkage Projects
ANIMAL BREEDING
动物饲养
  • 批准号:
    7459709
  • 财政年份:
    2007
  • 资助金额:
    $ 39万
  • 项目类别:
CORE--ANIMAL BREEDING AND SURGICAL FACILITY
核心——动物饲养和手术设施
  • 批准号:
    7486795
  • 财政年份:
    2007
  • 资助金额:
    $ 39万
  • 项目类别:
CORE--ANIMAL BREEDING AND SURGICAL FACILITY
核心——动物饲养和手术设施
  • 批准号:
    6909162
  • 财政年份:
    2005
  • 资助金额:
    $ 39万
  • 项目类别:
CORE--ANIMAL BREEDING AND SURGICAL FACILITY
核心——动物饲养和手术设施
  • 批准号:
    6576560
  • 财政年份:
    2002
  • 资助金额:
    $ 39万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了