Decidual T Cells in Immune-mediated Pregnancy Loss
蜕膜 T 细胞在免疫介导的妊娠丢失中的作用
基本信息
- 批准号:9107907
- 负责人:
- 金额:$ 22.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-15 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adoptive TransferAnimalsAntigensAntiphospholipid AntibodiesAntiphospholipid SyndromeAutoimmune DiseasesBlood VesselsCellsCharacteristicsComplicationDataDeciduaDendritic CellsFutureGoalsHealthHumanImmuneImmunizationIndividualInflammatoryLeadLeukocytesLipidsLupusLymphoidLymphoid TissueMHC Class I GenesMediatingMucous MembraneMusMyocardial InfarctionOrganOutcomePathogenesisPatientsPhenotypePhospholipidsPopulationPregnancyPregnancy OutcomePregnancy lossPregnant WomenProductionRecurrenceRoleStrokeSystemic Lupus ErythematosusT-LymphocyteThrombosisTranslatingUterusWild Type MouseWomanWorkantigen bindingbasecytokinefetalimplantationin vivokiller T cellmacrophagenovelperipheral bloodpregnant
项目摘要
DESCRIPTION (provided by applicant): The pregnant uterine mucosa, called decidua, contains ~15-30% of leukocytes in early pregnancy in humans. Recent studies have detected natural killer T cells in human and mouse decidua. The murine peri-implantation uterus contains an expanded population of natural killer T cells, but their function in pregnancy remains unclear. Natural killer T cells are known to react with lipid antigens bound to a non-classical MHC class I-like lipid antigen presenting molecule called CD1d. In preliminary work, we have identified T cells that react with phospholipid (PL) antigens in the decidua, and lymphoid organs of mice as well as in peripheral blood of humans. These novel PL-reactive T cells (PL-T) are relatively abundant in the decidua compared to lymphoid organs in mice and secrete cytokines upon immunization with PL antigens in vivo. The PL-T cells are restricted by CD1d. Such PL-T cells are relatively more in the decidua of lupus mice than in healthy strains. The goal of this R21 Exploratory proposal is to understand the role of PL-T cells in immune-mediated pregnancy loss. Guided by our novel observations, we hypothesize that PL-T cells are altered in lupus mice; such altered PL-T cells induce pregnancy loss. In Aim 1, we will determine the role of PL-T cells on pregnancy outcome in mice with lupus and anti-phospholipid syndrome. In Aim 2, we will begin to translate animal findings. Specifically, we will determine if PL-T cells exist in the
decidua of humans, and whether peripheral blood and decidual PL-T cells from patients with lupus/anti-phospholipid syndrome display an activated phenotype with increased production of pro-inflammatory cytokines compared to PL-T cells from normal pregnant women. It is hoped that the study will advance our understanding of decidual immune cells in fetal health and elucidate a novel pathogenetic mechanism of immune-mediated pregnancy loss in lupus and autoimmune diseases.
描述(申请人提供):怀孕的子宫粘膜,称为蜕膜,在人类怀孕早期含有约15%-30%的白细胞。最近的研究在人类和小鼠的蜕膜中发现了自然杀伤T细胞。小鼠着床期子宫含有大量自然杀伤T细胞,但它们在怀孕期间的功能尚不清楚。众所周知,自然杀伤T细胞与脂类抗原结合在一起,这种脂类抗原与一种名为CD1d的非经典MHC I类脂类抗原递呈分子相结合。在初步工作中,我们已经在小鼠的蜕膜、淋巴器官和人类的外周血液中发现了与磷脂(PL)抗原反应的T细胞。与淋巴器官相比,这些新型的PL反应性T细胞(PL-T)在小鼠的蜕膜中相对丰富,并在体内用PL抗原免疫后分泌细胞因子。PL-T细胞受CD1d的限制。这种PL-T细胞在狼疮小鼠的蜕膜中比在健康品系中相对更多。这项R21探索性建议的目的是了解PL-T细胞在免疫介导的妊娠丢失中的作用。在我们新的观察结果的指导下,我们假设狼疮小鼠的PL-T细胞发生了变化,这种变化导致了妊娠丢失。在目标1中,我们将确定PL-T细胞在狼疮和抗磷脂综合征小鼠妊娠结局中的作用。在目标2中,我们将开始翻译动物的发现。具体来说,我们将确定PL-T细胞是否存在于
与正常孕妇的PL-T细胞相比,狼疮/抗磷脂综合征患者的外周血和蜕膜PL-T细胞是否表现出激活的表型,其促炎细胞因子的产生增加。希望本研究能促进我们对蜕膜免疫细胞在胎儿健康中的认识,并阐明狼疮和自身免疫性疾病中免疫介导的妊娠丢失的新的发病机制。
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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Ram Raj Singh其他文献
Occurrence of autoimmune diseases and relationship of autoantibody expression with HLA phenotypes in multicase rheumatoid arthritis families.
多例类风湿性关节炎家系中自身免疫性疾病的发生及自身抗体表达与 HLA 表型的关系。
- DOI:
- 发表时间:
1993 - 期刊:
- 影响因子:2.1
- 作者:
V. Taneja;Ram Raj Singh;Anand N. Malaviya;C. Anand;Narinder K. Mehra - 通讯作者:
Narinder K. Mehra
Ram Raj Singh的其他文献
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{{ truncateString('Ram Raj Singh', 18)}}的其他基金
Role of Innate B1 B Cells in the Development of Diffuse Lung Hemorrhage
先天 B1 B 细胞在弥漫性肺出血发展中的作用
- 批准号:
9316608 - 财政年份:2016
- 资助金额:
$ 22.87万 - 项目类别:
Role of Innate B1 B Cells in the Development of Diffuse Lung Hemorrhage
先天 B1 B 细胞在弥漫性肺出血发展中的作用
- 批准号:
9182833 - 财政年份:2016
- 资助金额:
$ 22.87万 - 项目类别:
Decidual T Cells in Immune-mediated Pregnancy Loss
蜕膜 T 细胞在免疫介导的妊娠丢失中的作用
- 批准号:
8932614 - 财政年份:2015
- 资助金额:
$ 22.87万 - 项目类别:
Gender Bias in Lupus: Contribution of Sex Chromosomes
狼疮中的性别偏差:性染色体的贡献
- 批准号:
7903679 - 财政年份:2009
- 资助金额:
$ 22.87万 - 项目类别:
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