Autophagy in T lymphocyte function
T 淋巴细胞功能中的自噬
基本信息
- 批准号:8461210
- 负责人:
- 金额:$ 35.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-01 至 2015-04-30
- 项目状态:已结题
- 来源:
- 关键词:AgingAutoimmune DiseasesAutophagocytosisAutophagosomeCatabolic ProcessCell Cycle ProgressionCell DeathCell ProliferationCell SurvivalCell physiologyCessation of lifeCytosolDataDefectDevelopmentEukaryotic CellFundingFutureGenesHealthHomeostasisImmune responseInfectionLymphocyte FunctionMalignant NeoplasmsMature T-LymphocyteMediatingMembraneMitochondriaMolecularNerve DegenerationOrganellesPathologic ProcessesPhysiological ProcessesPlayProcessRoleStagingStructureT-Cell ProliferationT-LymphocyteTestingVaccine DesignVesicleWorkdesigndisorder preventioninsightmicrobialnovelpathogentumor
项目摘要
DESCRIPTION (provided by applicant): Macroautophagy (hereafter referred to as "autophagy") is a well-conserved catabolic process in eukaryotic cells. It is defined by the formation of double membrane autophagosome vesicles and functions in the intracellular degradation of cytosol and organelles. Although autophagy has long been recognized, its functions in various physiological and pathological processes have only begun to be elucidated. Our recent work has demonstrated that primary T lymphocytes have the capacity to undergo autophagy and that the autophagy gene Atg5 is essential for T cell survival and proliferation, suggesting that autophagy is a novel mechanism regulating mature T cell homeostasis. However, the underlying molecular mechanisms by which autophagy promotes T lymphocyte survival and proliferation remain unknown. Specifically, it is not clear whether the defect in Atg5-/- T cells is caused by an inability to form autophagosomes or an autophagy-independent function of Atg5? More importantly, if impaired autophagy compromises T cell survival, by what mechanism does autophagy inhibit death in T lymphocytes? Using conditional deletion of a second autophagy gene, Atg7, in T lymphocytes, we have established an essential role for autophagy in the survival of naive T lymphocytes. We have found that mitochondrial homeostasis is disrupted in T cells lacking Atg5 or Atg7. These results suggest that autophagy plays a key role in T cell function through maintaining the homeostasis of intracellular organelles. Our overall hypothesis is that autophagic function in mature primary T lymphocytes is required for cell survival and TCR-mediated proliferation through maintaining turnover of cytoplasmic material, in particular the essential organelle structures such as mitochondria. We proposed three specific aims to test this hypothesis. In aim 1, we will determine how autophagy is regulated in primary T lymphocytes and the developmental stages at which the induction of autophagy contributes to cell survival. In aim 2, we will examine how deregulation of organelle homeostasis contributes to cell death in autophagy-deficient primary T lymphocytes. In aim 3, we will establish the mechanisms by which loss of autophagy genes inhibits cell cycle progression during T cell proliferation. Results from this study will shed important insights to the molecular mechanisms by which mature T cell function is regulated. Better understanding this process will undoubtedly help future design of strategies boosting T cell immune responses to pathogens.
描述(由申请人提供):巨自噬(以下称为“自噬”)是真核细胞中非常保守的分解代谢过程。它通过形成双膜自噬体囊泡来定义,并在胞质溶胶和细胞器的细胞内降解中起作用。虽然自噬早已被认识,但其在各种生理和病理过程中的功能才刚刚开始阐明。我们最近的工作表明,原代T淋巴细胞有能力进行自噬和自噬基因Atg 5是T细胞的生存和增殖所必需的,这表明自噬是一种新的机制,调节成熟的T细胞的稳态。然而,自噬促进T淋巴细胞存活和增殖的潜在分子机制仍然未知。具体来说,目前尚不清楚Atg 5-/- T细胞的缺陷是由无法形成自噬体或Atg 5的自噬独立功能引起的?更重要的是,如果受损的自噬损害T细胞的存活,自噬通过什么机制抑制T淋巴细胞的死亡?在T淋巴细胞中使用第二个自噬基因Atg 7的条件性缺失,我们已经建立了自噬在幼稚T淋巴细胞存活中的重要作用。我们已经发现,线粒体稳态在缺乏Atg 5或Atg 7的T细胞中被破坏。这些结果表明,自噬通过维持细胞内细胞器的稳态在T细胞功能中起关键作用。我们的总体假设是,成熟的原代T淋巴细胞中的自噬功能是细胞存活和TCR介导的增殖所需的,通过维持细胞质物质的周转,特别是基本的细胞器结构,如线粒体。我们提出了三个具体目标来检验这一假设。在目标1中,我们将确定自噬在初级T淋巴细胞中是如何调节的,以及自噬诱导有助于细胞存活的发育阶段。在目标2中,我们将研究细胞器稳态失调如何导致自噬缺陷的原代T淋巴细胞的细胞死亡。在目标3中,我们将建立自噬基因的丢失在T细胞增殖期间抑制细胞周期进程的机制。这项研究的结果将为成熟T细胞功能调节的分子机制提供重要见解。更好地理解这一过程无疑将有助于未来设计增强T细胞对病原体免疫反应的策略。
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.
- DOI:10.4049/jimmunol.1100710
- 发表时间:2011-11-15
- 期刊:
- 影响因子:0
- 作者:McLeod IX;Zhou X;Li QJ;Wang F;He YW
- 通讯作者:He YW
Transfer of CD8+ T cell memory using Bcl-2 as a marker.
- DOI:10.4049/jimmunol.1103481
- 发表时间:2013-02-01
- 期刊:
- 影响因子:0
- 作者:Dunkle A;Dzhagalov I;Gordy C;He YW
- 通讯作者:He YW
Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression.
- DOI:10.1158/2159-8290.cd-15-1412
- 发表时间:2016-09
- 期刊:
- 影响因子:28.2
- 作者:Wang Y;Sun SN;Liu Q;Yu YY;Guo J;Wang K;Xing BC;Zheng QF;Campa MJ;Patz EF Jr;Li SY;He YW
- 通讯作者:He YW
Regulation of T-cell survival and mitochondrial homeostasis by TSC1.
- DOI:10.1002/eji.201141411
- 发表时间:2011-11
- 期刊:
- 影响因子:5.4
- 作者:O'Brien, Thomas F.;Gorentla, Balachandra K.;Xie, Danli;Srivatsan, Sruti;McLeod, Ian X.;He, You-Wen;Zhong, Xiao-Ping
- 通讯作者:Zhong, Xiao-Ping
Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes.
- DOI:10.4049/jimmunol.1001822
- 发表时间:2011-02-01
- 期刊:
- 影响因子:0
- 作者:Jia W;Pua HH;Li QJ;He YW
- 通讯作者:He YW
{{
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 }}
You-Wen He其他文献
You-Wen He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('You-Wen He', 18)}}的其他基金
The impact of genetic diversity among Akkermansia strains on the effectivenes of immune checkpoint inhibitors in cancer immunotherapies
阿克曼氏菌菌株遗传多样性对癌症免疫治疗中免疫检查点抑制剂有效性的影响
- 批准号:
10115682 - 财政年份:2020
- 资助金额:
$ 35.93万 - 项目类别:
A novel pathway regulating cytokine production and asthma development
调节细胞因子产生和哮喘发展的新途径
- 批准号:
7356481 - 财政年份:2009
- 资助金额:
$ 35.93万 - 项目类别:
A novel pathway regulating cytokine production and asthma development
调节细胞因子产生和哮喘发展的新途径
- 批准号:
7843494 - 财政年份:2009
- 资助金额:
$ 35.93万 - 项目类别:
BcI-2 family in T lymphocyte homeostasis
Bcl-2 家族在 T 淋巴细胞稳态中的作用
- 批准号:
8389558 - 财政年份:2008
- 资助金额:
$ 35.93万 - 项目类别:
Function of thymic epithelial cells in T lymphocyte maturation
胸腺上皮细胞在T淋巴细胞成熟中的功能
- 批准号:
7686243 - 财政年份:2008
- 资助金额:
$ 35.93万 - 项目类别:
BcI-2 family in T lymphocyte homeostasis
Bcl-2 家族在 T 淋巴细胞稳态中的作用
- 批准号:
7580414 - 财政年份:2008
- 资助金额:
$ 35.93万 - 项目类别:
相似国自然基金
Autoimmune diseases therapies: variations on the microbiome in rheumatoid arthritis
- 批准号:31171277
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
相似海外基金
Autoantibodies and antibody-secreting cells in neurological autoimmune diseases: from biology to therapy
神经性自身免疫性疾病中的自身抗体和抗体分泌细胞:从生物学到治疗
- 批准号:
479128 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Operating Grants
Effects of maternal immune activation on autoimmune diseases in offsprings
母体免疫激活对后代自身免疫性疾病的影响
- 批准号:
23H02155 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
IPP: AUTOIMMUNE DISEASES STATISTICAL AND CLINICAL COORDINATING CENTER (ADSCCC)
IPP:自身免疫性疾病统计和临床协调中心 (ADSCCC)
- 批准号:
10788032 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Biomarkers of vascular endothelial dysfunction in systemic autoimmune diseases: analysis of circulating microRNAs
系统性自身免疫性疾病中血管内皮功能障碍的生物标志物:循环 microRNA 分析
- 批准号:
23K14742 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
NOVEL HUMORAL AND CELLULAR BIOMARKERS OF AUTOIMMUNE DISEASES CAUSED BY IMMUNOTHERAPY
免疫治疗引起的自身免疫性疾病的新型体液和细胞生物标志物
- 批准号:
10593224 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Structural mechanisms of autoimmune diseases targeting cys-loop receptors
针对半胱氨酸环受体的自身免疫性疾病的结构机制
- 批准号:
10864719 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Developing non-immunosuppressive immune-based therapeutics for targeted treatment of autoimmune diseases
开发非免疫抑制性免疫疗法来靶向治疗自身免疫性疾病
- 批准号:
10586562 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Regulation of autoimmune diseases by PTPN22 phosphatase
PTPN22磷酸酶对自身免疫性疾病的调节
- 批准号:
23K06589 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Decipher and target GABA metabolism and GABA receptor-mediated signaling in autoimmune diseases
破译并靶向自身免疫性疾病中的 GABA 代谢和 GABA 受体介导的信号传导
- 批准号:
10623380 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别:
Targeting the long isoform of the prolactin receptor to treat autoimmune diseases and B-cell malignancies
靶向催乳素受体的长亚型来治疗自身免疫性疾病和 B 细胞恶性肿瘤
- 批准号:
10735148 - 财政年份:2023
- 资助金额:
$ 35.93万 - 项目类别: