ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
基本信息
- 批准号:10216997
- 负责人:
- 金额:$ 55.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-13 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:Activities of Daily LivingAffectBiologicalBlood VesselsCRISPR/Cas technologyCellular biologyClinicalDecidual Cell ReactionsDependenceEpidemiologyEvolutionFamilyFetal TissuesFetusGene TargetingGenesGenotypeGoalsHomeHumanIndividualKnockout MiceLaboratoriesLeadLeukocytesLigandsMaternal-Fetal ExchangeMusNatural Killer CellsOrganOutcomePlacentationPlayPre-EclampsiaPregnancyPregnancy OutcomePregnant UterusProcessPropertyReceptor CellReproductionRoleTimeTissuesUterusepidemiology studyexperimental studyfetalgenome editingin vivoinsightkiller immunoglobulin-like receptorpregnancy disorderpregnantreceptortranscription factor
项目摘要
Epidemiological studies have associated preeclampsia outcomes with genotypes of receptors on maternal
natural killer (NK) cells, and genotypes of their cognate HLA class I (HLA-I) ligands in fetuses. These clinical
findings have been replicated and strongly suggest that uterine NK (uNK) cells, the most abundant leukocytes
at the maternal-fetal interface, specifically use their receptors to recognize HLA-I on fetal tissues, thereby
playing vital roles in normal placentation, probably by affecting the vasculature which is abnormal in
preeclampsia. Although it is challenging to study these possibilities in human reproduction, and we
acknowledge that there are species-specific differences between human and mouse pregnancy, studies of
mouse NK cells can yield important conceptual insight, as demonstrated numerous times previously in NK
cell biology. Recent studies from the applicant's laboratory indicate that mouse organs, including the virgin
uterus, contain both circulating “conventional” NK (cNK) cells and tissue-resident NK (trNK) cells that reside
in the organ and do not recirculate. cNK and trNK cells from different organs represent distinct lineages of NK
cells because they have differences in transcription factor dependencies. Moreover, cNK and trNK cells have
different functional capacities. Finally, the Ly49 family of receptors are the functional equivalents to the human
NK cell receptors implicated in preeclampsia. These considerations lead to the following proposed Specific
Aims: 1) Determine contributions of cNK and trNK cells to uNK cells in pregnancy and decidualization; 2)
Examine transcription factor dependence of uNK cells; and 3) Determine role of Ly49 receptors in pregnancy.
Thus, these studies will provide major insight into the role of uNK cells in pregnancy, the major long-term
objective of this proposal.
流行病学研究表明,先兆子痫的结局与母体受体的基因型有关。
自然杀伤(NK)细胞及其同源人类白细胞抗原I类(HL A-I)配体在胎儿中的基因分型。这些临床
研究结果得到了复制,并强烈表明,子宫NK(Unk)细胞是最丰富的白细胞
在母胎界面,特异性地利用它们的受体识别胎儿组织上的人类白细胞抗原-I,从而
在正常胎盘形成中发挥重要作用,可能是通过影响血管系统
先兆子痫。尽管研究人类生殖中的这些可能性是具有挑战性的,而且我们
承认人类和小鼠怀孕之间存在物种特异性差异,研究
小鼠NK细胞可以产生重要的概念洞察力,正如之前在NK细胞中多次证明的那样
细胞生物学。申请人实验室最近的研究表明,包括处女在内的小鼠器官
子宫中既有循环中的“常规”NK(CNK)细胞,也有驻留在子宫中的组织驻留NK(TrNK)细胞
而且不会再循环。来自不同器官的CNK和trNK细胞代表不同的NK谱系
细胞,因为它们对转录因子的依赖程度不同。此外,CNK和trNK细胞具有
不同的功能能力。最后,Ly49受体家族在功能上等同于人类
NK细胞受体与子痫前期有关。这些考虑导致了以下拟议的具体方案
目的:1)确定CNK和trNK细胞在妊娠和蜕膜形成过程中对Unk细胞的贡献;2)
检测Unk细胞对转录因子的依赖;以及3)确定Ly49受体在妊娠中的作用。
因此,这些研究将提供对Unk细胞在妊娠中的作用的主要洞察,这是长期的主要
这项提案的目标。
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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Wayne M. Yokoyama其他文献
Immune functions encoded by the natural killer gene complex
自然杀伤基因复合体编码的免疫功能
- DOI:
10.1038/nri1055 - 发表时间:
2003-04-01 - 期刊:
- 影响因子:60.900
- 作者:
Wayne M. Yokoyama;Beatrice F. M. Plougastel - 通讯作者:
Beatrice F. M. Plougastel
The mother-child union: the case of missing-self and protection of the fetus.
母子结合:自我缺失与胎儿保护案例
- DOI:
- 发表时间:
1997 - 期刊:
- 影响因子:11.1
- 作者:
Wayne M. Yokoyama - 通讯作者:
Wayne M. Yokoyama
Expression of a single inhibitory Ly49 receptor is sufficient to license NK cells for effector functions
单一抑制性 Ly49 受体的表达足以许可 NK 细胞发挥效应功能
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Sytse J. Piersma;Shasha Li;Pamela Wong;Michael D. Bern;Jennifer Poursine‐Laurent;Liping Yang;D. L. Beckman;Bijal A. Parikh;Wayne M. Yokoyama - 通讯作者:
Wayne M. Yokoyama
Structural basis of MHCI antigen presentation sabotage by cowpox CPXV203
- DOI:
10.1016/j.molimm.2012.02.034 - 发表时间:
2012-05-01 - 期刊:
- 影响因子:
- 作者:
William H. McCoy;Xiaoli Wang;Wayne M. Yokoyama;Ted H. Hansen;Daved Fremont - 通讯作者:
Daved Fremont
Catch us if you can
如果你能就抓住我们
- DOI:
10.1038/419679a - 发表时间:
2002-10-17 - 期刊:
- 影响因子:48.500
- 作者:
Wayne M. Yokoyama - 通讯作者:
Wayne M. Yokoyama
Wayne M. Yokoyama的其他文献
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{{ truncateString('Wayne M. Yokoyama', 18)}}的其他基金
Infectious Disease/Immunology Stimulating Access to Research in Residency (ID/IMM StARR) Program at Washington University
华盛顿大学传染病/免疫学促进住院医师研究 (ID/IMM StARR) 项目
- 批准号:
10592699 - 财政年份:2023
- 资助金额:
$ 55.78万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
10451584 - 财政年份:2018
- 资助金额:
$ 55.78万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
9762839 - 财政年份:2018
- 资助金额:
$ 55.78万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
9980287 - 财政年份:2018
- 资助金额:
$ 55.78万 - 项目类别:
Natural Killer Cell Control of Murine Cytomegalovirus Infection
自然杀伤细胞控制鼠巨细胞病毒感染
- 批准号:
10444730 - 财政年份:2017
- 资助金额:
$ 55.78万 - 项目类别:
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