GSK3b and dsRNA in CD8 cells
CD8 细胞中的 GSK3b 和 dsRNA
基本信息
- 批准号:10536526
- 负责人:
- 金额:$ 23.33万
- 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:2022-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Autoimmune DiseasesCD8-Positive T-LymphocytesCellsDouble-Stranded RNAFailureGAG GeneGTP-Binding Protein alpha Subunits, GsHexachlorobenzeneHomeostasisImmune responseInfectionInnate Immune ResponseInterferonsMitochondriaMolecularPathway interactionsPatternPhosphorylationPlayProductionRegulationRoleSourceT cell responseT-LymphocyteTestingTranscriptVirusVirus Diseasescytokinenovelpathogenresponse
项目摘要
PROJECT SUMMARY
Double-stranded RNA (dsRNA) is a well-known pathogen-associated molecular pattern (PAMP)
generated during viral infections that triggers the innate immune response and plays a critical role in virus
protection through the direct effect on type I IFN. However, in recent years it has been clear that this pathway
can also be induced by endogenous dsRNA, with mitochondria transcripts being one of the major sources of
endogenous dsRNA. The presence of endogenous dsRNA suggests that there must be mechanisms in place to
keep on check their accumulation to avoid triggering RLRs pathways. Although there is a number of studies on
how the production of type I IFN resulting from endogenous dsRNA can indirectly modulate T cell response, no
previous studies have examined dsRNA in T cells. Our recent studies have revealed the presence of endogenous
dsRNA in CD8 cells upon activation, and mitochondria seems to be the primary source. In addition, we identify
a new mechanism that CD8 cells use to restrict the levels of dsRNA generated: inactivation of mitochondria
GSK3 by phosphorylation on Ser389. Interestingly, failure to inactivate GSK3 by phospho-Ser389 results in a
greater accumulation of mitochondrial dsRNA in activated CD8 cells. Importantly, we also found that failure to
inactivate GSK3 by phospho-Ser389 results in higher levels of IFN produced by CD8 cells. We hypothesize that
mitochondrial dsRNAs are generated during activation of CD8 cells, can trigger the RLR pathway and contribute
to sustain IFN production. We also propose that mitochondrial GSK3 interferes with the mitochondrial
degradosome and that inactivation of mitochondrial GSK3 through phosphorylation on Ser389 in response to
dsRNA is essential for maintaining dsRNA-homeostasis and restricting IFN production. We will test this
hypothesis with the following specific aims: 1) to show that mitochondrial dsRNA is generated during activation
of CD8 cells and contributes to the production of IFN. 2) to show that inactivation of GSK3 through Ser389-
phosphorylation plays a role in the homeostasis of mitochondrial dsRNA during activation of CD8 cells. The
results from the proposed studies could be a major breakthrough since they will show how endogenous dsRNA
can contribute to sustain cytokine production in activated CD8 cells, and its potential impact on autoimmune
disease.
项目总结
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)
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Mercedes Rincon其他文献
Mercedes Rincon的其他文献
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{{ truncateString('Mercedes Rincon', 18)}}的其他基金
Enhancing mitochondrial metabolism to improve anti-tumor CD8 immune response
增强线粒体代谢,提高抗肿瘤CD8免疫反应
- 批准号:
10578743 - 财政年份:2022
- 资助金额:
$ 23.33万 - 项目类别:
Targeting mitochondrial regulator MCJ to enhance CD8 cell immune response
靶向线粒体调节剂 MCJ 增强 CD8 细胞免疫反应
- 批准号:
10293952 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
Fine-tuning of mitochondrial Complex I activity in CD8 cells
CD8 细胞中线粒体复合物 I 活性的微调
- 批准号:
10092947 - 财政年份:2020
- 资助金额:
$ 23.33万 - 项目类别:
Fostering entrepreneurship in biomedical research
培养生物医学研究创业精神
- 批准号:
8998210 - 财政年份:2016
- 资助金额:
$ 23.33万 - 项目类别:
IL-6: an innate immune regulator for the plasticity of Tfh cells
IL-6:Tfh 细胞可塑性的先天免疫调节剂
- 批准号:
8434542 - 财政年份:2012
- 资助金额:
$ 23.33万 - 项目类别:
COBRE: UVT: CORE TRANSGENIC ANIMAL PROGRAM: MOUSE GENOMIC DNA BAC LIBRARY
COBRE:UVT:核心转基因动物计划:小鼠基因组 DNA BAC 文库
- 批准号:
7959621 - 财政年份:2009
- 资助金额:
$ 23.33万 - 项目类别:
MCJ function in mouse mammary tumor properties
MCJ 在小鼠乳腺肿瘤特性中的功能
- 批准号:
7807612 - 财政年份:2008
- 资助金额:
$ 23.33万 - 项目类别:
COBRE: UVT: CORE TRANSGENIC ANIMAL PROGRAM: MOUSE GENOMIC DNA BAC LIBRARY
COBRE:UVT:核心转基因动物计划:小鼠基因组 DNA BAC 文库
- 批准号:
7720875 - 财政年份:2008
- 资助金额:
$ 23.33万 - 项目类别:
MCJ function in mouse mammary tumor properties
MCJ 在小鼠乳腺肿瘤特性中的功能
- 批准号:
7390544 - 财政年份:2008
- 资助金额:
$ 23.33万 - 项目类别:
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