Analysis of MyD88-mediated immune activation in Sjogren's syndrome pathogenesis

MyD88介导的免疫激活在干燥综合征发病机制中的分析

基本信息

项目摘要

Project Summary/ Abstract Sjögren's syndrome (SS) is an autoimmune disease in which exocrine tissue is damaged, resulting in loss of tears and saliva production. The diagnosis of SS is challenging and patients often experience symptoms for years before they are diagnosed. Once diagnosis is achieved, no SS-specific curative treatment options are available; rather treatments for SS are palliative. Thus, there is a critical need to identify etiologic events that will facilitate earlier diagnosis of SS and mitigate or abrogate the progression of this debilitating disease. Even though the immune system drives SS, few mechanistic studies of the seminal factors responsible for SS are reported. Studies in lupus, a related autoimmune disease, demonstrated that Myeloid Differentiation Factor Primary Response Protein 88 (MyD88) is critical for disease development. MyD88 is an adaptor molecule that is expressed ubiquitously and is required for most Toll-like receptor (TLR) signaling. Notably, TLRs are elevated locally (in salivary tissue) and in peripheral blood cells of SS patients, suggesting TLR signaling contributes to SS pathogenesis. Surprisingly, the role of MyD88 and TLR signaling has not been evaluated in depth in SS. Our central HYPOTHESES are that MyD88 expression in salivary tissue and in immune cells is crucial for SS initiation and progression and that TLR signals via MyD88 drive SS pathogenesis. Our OBJECTIVE is to evaluate the means by which MyD88-mediated signaling contributes to SS and to identify specific factors that activate TLR signaling pathways in SS. We will use a SS mouse model (NOD.B10) and our recently developed knockout strain of NOD.B10 mice that lack MyD88. These mice provide the opportunity to examine the role of MyD88 in SS. We will test our hypotheses through the following Specific Aims: (1) To determine whether MyD88 expression by hematopoietic cells is required for SS pathogenesis. These experiments will examine autoantibody production and salivary function to determine whether hematopoietic-intrinsic MyD88 expression is crucial for specific SS disease manifestations. (2) To evaluate the role of MyD88 in the generation and pathogenicity of autoantibodies in SS. These results will identify the role of MyD88 in the development of autoantibodies in SS, and will establish whether antibodies derived from MyD88-/- NOD.B10 mice have reduced pathogenicity in vivo. (3) To investigate the role of MyD88-dependent TLR2/4 activation in SS. We will determine whether signaling via TLR2/4 in salivary tissue contributes to SS in a MyD88-dependent manner. We will also overexpress a specific damage-associated molecular pattern that activates TLR2/4 in a MyD88-dependent manner to determine whether this accelerates SS. Finally, we will assess TLR2 and TLR4 blockade in SS to determine whether these attenuate disease. This study is innovative in that it will employ a novel mouse model to evaluate the role of MyD88, a key immune signaling molecule, in SS. The proposal is significant, as it will provide new knowledge regarding the role of MyD88 and TLR2/4 signaling in SS initiation and progression. This work will lay the foundation for future studies to identify therapeutics for patients with SS and other autoimmune diseases that target TLR/MyD88-related pathways.
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 }}

Jill Marie Kramer其他文献

Jill Marie Kramer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('Jill Marie Kramer', 18)}}的其他基金

Analysis of MyD88-mediated immune activation in Sjogrens syndrome pathogenesis
MyD88介导的干燥综合征发病机制中的免疫激活分析
  • 批准号:
    10363733
  • 财政年份:
    2020
  • 资助金额:
    $ 35.74万
  • 项目类别:
Analysis of MyD88-mediated immune activation in Sjogrens syndrome pathogenesis
MyD88介导的干燥综合征发病机制中的免疫激活分析
  • 批准号:
    10599234
  • 财政年份:
    2020
  • 资助金额:
    $ 35.74万
  • 项目类别:
Analysis of MyD88-mediated immune activation in Sjogrens syndrome pathogenesis
MyD88介导的干燥综合征发病机制中的免疫激活分析
  • 批准号:
    10133046
  • 财政年份:
    2020
  • 资助金额:
    $ 35.74万
  • 项目类别:
Analysis of the role of IgM in Sjogrens syndrome
IgM在干燥综合征中的作用分析
  • 批准号:
    9507227
  • 财政年份:
    2018
  • 资助金额:
    $ 35.74万
  • 项目类别:
Autoantibodies and B Cell Chemotaxis in Sjogren's Syndrome
干燥综合征中的自身抗体和 B 细胞趋化性
  • 批准号:
    8064721
  • 财政年份:
    2010
  • 资助金额:
    $ 35.74万
  • 项目类别:
Autoantibodies and B Cell Chemotaxis in Sjogren's Syndrome
干燥综合征中的自身抗体和 B 细胞趋化性
  • 批准号:
    8292245
  • 财政年份:
    2010
  • 资助金额:
    $ 35.74万
  • 项目类别:
Autoantibodies and B Cell Chemotaxis in Sjogren's Syndrome
干燥综合征中的自身抗体和 B 细胞趋化性
  • 批准号:
    8672624
  • 财政年份:
    2010
  • 资助金额:
    $ 35.74万
  • 项目类别:
Autoantibodies and B Cell Chemotaxis in Sjogren's Syndrome
干燥综合征中的自身抗体和 B 细胞趋化性
  • 批准号:
    8484386
  • 财政年份:
    2010
  • 资助金额:
    $ 35.74万
  • 项目类别:
Autoantibodies and B Cell Chemotaxis in Sjogren's Syndrome
干燥综合征中的自身抗体和 B 细胞趋化性
  • 批准号:
    8599931
  • 财政年份:
    2010
  • 资助金额:
    $ 35.74万
  • 项目类别:
Autoantibodies and B Cell Chemotaxis in Sjogren's Syndrome
干燥综合征中的自身抗体和 B 细胞趋化性
  • 批准号:
    7871645
  • 财政年份:
    2010
  • 资助金额:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 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:
    $ 35.74万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了