Mechanisms of Tolerance to Renal Maternal Microchimerism
肾母体微嵌合的耐受机制
基本信息
- 批准号:7671281
- 负责人:
- 金额:$ 38.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-13 至 2012-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAllelesAlloantigenAntigen TargetingAntigen-Presenting CellsAntigensApoptoticAtypical lymphocyteAutoimmune DiseasesAutoimmunityBiological AssayBloodBlood CellsBlood specimenCardiac MyocytesCell CommunicationCellsChildChildhoodChronicCross PresentationDNADataDermatomyositisDiseaseDisease remissionEpithelial CellsFetusFlareFlow CytometryFutureGenomicsHematological DiseaseHematopoieticHepatocyteHistocompatibility AntigensIL2RA geneImmune ToleranceImmune systemImmunosuppressionIn VitroIndividualInfantInflammationInflammatoryInterleukin-10Interleukin-4InvestigationKidneyLeadLifeLymphocyteMicrochimerismModelingNecrosisNephritisNewly Diagnosed DiseaseOrganPatientsPeptidesPeripheralPeripheral Blood Mononuclear CellPregnancyProductionRegulationResearch PersonnelResearch ProposalsRoleSourceStagingSurfaceSystemic Lupus ErythematosusSystemic SclerodermaT-LymphocyteTestingTimeTissuesTubular formationcytokinedisorder controlfetalin vivoprogramsresponsetrend
项目摘要
DESCRIPTION (provided by applicant): The proposal's overall objective is to test mechanisms by which maternal microchimerism may contribute to chronic inflammation in systemic lupus erythematosus nephritis (SLE-N). Elevated levels of fetal and maternal microchimerism (MMc) have been found within blood and tissues of patients with systemic sclerosis, SLE, and dermatomyositis. However, microchimerism is also common in healthy individuals. Moreover, previous studies were not able to control for disease activity or immunosuppression, which may affect tolerance to chimeric cells. The PI has found maternal cells in infant organs differentiated into hematopoietic cells, cardiac myocytes, hepatocytes, and renal tubular epithelial cells. Long-term persistence to MMc implies immune tolerance, and loss of tolerance to MMc may lead to chronic inflammation within target organs harboring maternal cells. The Pi's preliminary data suggests that peripheral T lymphocytes from pediatric SLE patients are hyper-reactive to maternal cells. Moreover, SLE patients showed a trend toward decreased MMc in the blood. Thus, host lymphocytes reactive to maternal antigens within tissues may also clear maternal cells from the blood. This study will be the first to directly test the correlation of MMc in blood with SLE disease activity and immunosuppression. In addition, we will test a mechanistic model for how maternal cells bearing alloantigens may stimulate the host immune system to contribute to chronic inflammatory disease. Specific Aim #1 will test the hypothesis that levels of MMc in blood correlate with disease activity and immunosuppression in pediatric patients with SLE-N. Specific Aim #2 will investigate direct T lymphocyte alloreactivity to maternal antigens in SLE-N patients compared to controls. Tolerance to maternal antigen presenting cells will be tested for correlations with disease activity, immunosuppression, and presence or absence of MMc. Specific Aim #3 will investigate indirect T lymphocyte alloreactivity to maternal antigens presented by host APC in SLE-N patients compared with controls using apoptotic or necrotic maternal cells as sources of maternal antigens. Specific Aim #4 will test the role of T regulatory cells in tolerance to maternal antigens. The finding that maternal cells are targets forT lymphocytes in SLE patients would lead to future investigations to determine which antigens are targeted. Peptides blocking host- maternal cell interactions in vitro could potentially be used in vivo as specific treatments for SLE nephritis.
描述(由申请人提供):该提案的总体目标是测试母体微嵌合体可能导致系统性红斑狼疮肾炎(SLE-N)慢性炎症的机制。在系统性硬化症、SLE和皮肌炎患者的血液和组织中发现胎儿和母体微嵌合体(MMc)水平升高。然而,微嵌合体在健康个体中也很常见。此外,以前的研究不能控制疾病活动或免疫抑制,这可能会影响嵌合细胞的耐受性。PI发现婴儿器官中的母体细胞分化为造血细胞、心肌细胞、肝细胞和肾小管上皮细胞。对MMc的长期持续性意味着免疫耐受,对MMc的耐受性丧失可能导致携带母体细胞的靶器官内的慢性炎症。PI的初步数据表明,来自儿童SLE患者的外周血T淋巴细胞对母体细胞具有高反应性。此外,SLE患者血液中MMc呈下降趋势。因此,组织内与母体抗原反应的宿主淋巴细胞也可以从血液中清除母体细胞。本研究将首次直接检测血液中MMc与SLE疾病活动性和免疫抑制的相关性。此外,我们将测试一种机制模型,以了解携带同种异体抗原的母体细胞如何刺激宿主免疫系统,从而导致慢性炎症性疾病。具体目标#1将检验血液中MMc水平与SLE-N儿科患者的疾病活动性和免疫抑制相关的假设。具体目标#2将研究与对照相比,SLE-N患者中T淋巴细胞对母体抗原的直接同种异体反应性。将检测对母体抗原呈递细胞的耐受性与疾病活动、免疫抑制和是否存在MMc的相关性。具体目标#3将使用凋亡或坏死的母体细胞作为母体抗原的来源,与对照组相比,研究SLE-N患者中T淋巴细胞对宿主APC呈递的母体抗原的间接同种异体反应性。具体目标#4将测试T调节细胞在对母体抗原耐受性中的作用。母源细胞是SLE患者T淋巴细胞的靶细胞,这一发现将导致未来的研究以确定靶抗原。在体外阻断宿主-母体细胞相互作用的肽可能在体内用作SLE肾炎的特异性治疗。
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 }}
ANNE Marguerite STEVENS其他文献
ANNE Marguerite STEVENS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('ANNE Marguerite STEVENS', 18)}}的其他基金
Mechanisms of Tolerance to Renal Maternal Microchimerism
肾母体微嵌合的耐受机制
- 批准号:
7870914 - 财政年份:2009
- 资助金额:
$ 38.82万 - 项目类别:
Mechanisms of Tolerance to Renal Maternal Microchimerism
肾母体微嵌合的耐受机制
- 批准号:
7497557 - 财政年份:2007
- 资助金额:
$ 38.82万 - 项目类别:
Mechanisms of Tolerance to Renal Maternal Microchimerism
肾母体微嵌合的耐受机制
- 批准号:
7896579 - 财政年份:2007
- 资助金额:
$ 38.82万 - 项目类别:
Mechanisms of Tolerance to Renal Maternal Microchimerism
肾母体微嵌合的耐受机制
- 批准号:
7319358 - 财政年份:2007
- 资助金额:
$ 38.82万 - 项目类别:
Mechanisms of Tolerance to Renal Maternal Microchimerism
肾母体微嵌合的耐受机制
- 批准号:
8120758 - 财政年份:2007
- 资助金额:
$ 38.82万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政策的情绪动态
- 批准号:
10108433 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
- 批准号:
MR/X032809/1 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
- 批准号:
MR/X034690/1 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Fellowship
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341426 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341424 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Continuing Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
- 批准号:
2335955 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Standard Grant
The economics of (mis)information in the age of social media
社交媒体时代(错误)信息的经济学
- 批准号:
DP240103257 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Discovery Projects
How age & sex impact the transcriptional control of mammalian muscle growth
你多大
- 批准号:
DP240100408 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Discovery Projects
Supporting teachers and teaching in the age of Artificial Intelligence
支持人工智能时代的教师和教学
- 批准号:
DP240100111 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Discovery Projects
Enhancing Wahkohtowin (Kinship beyond the immediate family) Community-based models of care to reach and support Indigenous and racialized women of reproductive age and pregnant women in Canada for the prevention of congenital syphilis
加强 Wahkohtowin(直系亲属以外的亲属关系)以社区为基础的护理模式,以接触和支持加拿大的土著和种族育龄妇女以及孕妇,预防先天梅毒
- 批准号:
502786 - 财政年份:2024
- 资助金额:
$ 38.82万 - 项目类别:
Directed Grant