Transcriptional Regulation of Innate T cell fate
先天 T 细胞命运的转录调控
基本信息
- 批准号:10283893
- 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:2021
- 资助国家:美国
- 起止时间:2021-07-14 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adaptive Immune SystemAllergicAnimal ModelAntigen-Presenting CellsAntigensAutoimmunityBacteriaBee VenomsCD1 AntigensCD3 AntigensCell LineageCellsChromatinCollectionCytotoxic T-LymphocytesDataDevelopmentDiseaseEpigenetic ProcessEventExposure toFamilyFamily memberGenetic TranscriptionGlycolipidsHealthHumanImmuneImmune responseImmunityIn VitroInflammatoryInstructionJointsKnowledgeLeadLinkMediatingMolecularMucous MembraneMusMycobacterium tuberculosisNatural ImmunityOutputPeripheralPopulationProcessRNAReceptor ActivationReceptor SignalingResolutionRhus radicansRoleSLAM proteinShapesSignal TransductionSnake VenomsSpecificitySystemT-Cell DevelopmentT-Cell ReceptorT-LymphocyteTestingTherapeutic InterventionTherapeutic UsesThymus GlandTissuesTranscriptional RegulationVirusVitaminsZNF145 geneadaptive immunityconsumer productcytokineepigenetic regulationepigenomehuman diseaseimmunoregulationimprovedneonatal humannovelnovel therapeutic interventionpathogen exposureprecursor cellprogramsreceptorreceptor functionresidenceresponsetherapeutic candidatethymocytetranscription factortranscriptometumor
项目摘要
Project Summary
InnateT cells are a collection of T cells withimportant regulatory functions that have a crucial role in immunity
towards tumors, bacteria, viruses, and in cell-mediated autoimmunity. Due
large quantities of cytokines upon activation,
immune
response
populations
glycolipid
cells
T
commitment
to
innate T cells act as bridges between the innate and adaptive
systems a nd ontribute greatly In mice, this swiftness of
reflects their acquisition f functionality during their development in the thymus. Three major
within the innate T cell group are recognized namely, the invariant NKT cells that recognize
antigens presented by non-polymorphic CD1d molecules, the mucosal associated invariant T (MAIT)
that recognize vitamin metabolites presented by the non-polymorphic MR1 molecules, and the certain
cells which antigen specificities remain uncertain. We have established an in vitro system t hat mimics the
of double positive precursor cells to the innate T cell lineage and we propose to
their ability to promptly secrete
c to immune regulation and host protection.
o
,
deconstruct the
early transcriptional and epigenetic events that accompany this fate commitment (Aim 1). In this way, we will
identify
manipulation
early factors that influence innate T cell development, providing the possibility for selective
of innate T cell lineage specification. We will then investigatewhether human innate T cells
acquire an innate-like transcriptional program in the thymus similarly to their mouse counterparts and whether
this program is shared between the two species. To do so, we will profile the transcriptomes of iNKT and MAIT
cells purified from neonatal human thymi at the single cell level. In addition, we will extend our knowledge of
innate T cell lineage commitment by also studying CD1a-restricted T cells, which do not exist in mice (Aim 2).
Given their capacity to link key inflammatory axes of innate and adaptive immunity, a better understanding of
the molecular basis underpinning innate T cell development and plasticity, and how much this feature accounts
for their pathophysiological roles, is critical for developing novel therapeutic approaches.
项目摘要
先天性T细胞是具有重要调节功能的T细胞的集合,在免疫中具有至关重要的作用
针对肿瘤、细菌、病毒和细胞介导的自身免疫。由于
激活后产生大量细胞因子,
免疫
响应
人口
糖脂
细胞
不
承诺
到
先天性T细胞是先天性和适应性T细胞之间的桥梁。
在小鼠中,
反映了它们在胸腺发育期间获得的功能。三大
在先天性T细胞群内的NKT细胞被识别,即识别
由非多态性CD1d分子、粘膜相关不变T(MAIT)呈递的抗原
识别由非多态性MR1分子呈现的维生素代谢物,
抗原特异性仍然不确定的细胞。我们已经建立了一个体外系统,
双阳性前体细胞的先天性T细胞谱系,我们建议,
它们迅速分泌
c.免疫调节和宿主保护。
O
,
解构
早期转录和表观遗传事件伴随着这种命运的承诺(目标1)。以此来
识别
操纵
影响先天性T细胞发育的早期因素,为选择性免疫提供了可能性。
先天性T细胞谱系的特化。然后我们将研究人类先天性T细胞
在胸腺中获得类似于小鼠的先天转录程序,
这个程序是两个物种共享的。为此,我们将分析iNKT和MAIT的转录组,
在单细胞水平从新生人胸腺纯化的细胞。此外,我们将扩大我们的知识,
先天性T细胞谱系定型也通过研究小鼠中不存在的CD1a限制性T细胞(Aim 2)。
鉴于它们能够连接先天性和适应性免疫的关键炎症轴,
支持先天T细胞发育和可塑性的分子基础,以及这一特征在多大程度上解释了
对于开发新的治疗方法至关重要。
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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Laurent Gapin其他文献
Laurent Gapin的其他文献
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{{ truncateString('Laurent Gapin', 18)}}的其他基金
Transcriptional Regulation of Innate T cell fate
先天 T 细胞命运的转录调控
- 批准号:
10450153 - 财政年份:2021
- 资助金额:
$ 23.33万 - 项目类别:
Genetic determinants of "innate" T lymphocytes development and homeostasis
“先天”T 淋巴细胞发育和稳态的遗传决定因素
- 批准号:
10412121 - 财政年份:2021
- 资助金额:
$ 23.33万 - 项目类别:
Role of MAIT cells in a mouse model of spontaneous colitis
MAIT细胞在自发性结肠炎小鼠模型中的作用
- 批准号:
10436375 - 财政年份:2021
- 资助金额:
$ 23.33万 - 项目类别:
Role of MAIT cells in a mouse model of spontaneous colitis
MAIT细胞在自发性结肠炎小鼠模型中的作用
- 批准号:
10300940 - 财政年份:2021
- 资助金额:
$ 23.33万 - 项目类别:
Genetic determinants of "innate" T lymphocytes development and homeostasis
“先天”T 淋巴细胞发育和稳态的遗传决定因素
- 批准号:
10251641 - 财政年份:2021
- 资助金额:
$ 23.33万 - 项目类别:
TCR signal strength and iNKT cell subset development
TCR 信号强度和 iNKT 细胞亚群发育
- 批准号:
10447807 - 财政年份:2018
- 资助金额:
$ 23.33万 - 项目类别:
TCR signal strength and iNKT cell subset development
TCR 信号强度和 iNKT 细胞亚群发育
- 批准号:
9981614 - 财政年份:2018
- 资助金额:
$ 23.33万 - 项目类别:
TCR signal strength and iNKT cell subset development
TCR 信号强度和 iNKT 细胞亚群发育
- 批准号:
9761964 - 财政年份:2018
- 资助金额:
$ 23.33万 - 项目类别:
TCR signal strength and iNKT cell subset development
TCR 信号强度和 iNKT 细胞亚群发育
- 批准号:
10219060 - 财政年份:2018
- 资助金额:
$ 23.33万 - 项目类别:
Role of mCD1D2 in iNKT cell development and functions
mCD1D2 在 iNKT 细胞发育和功能中的作用
- 批准号:
9431944 - 财政年份:2018
- 资助金额:
$ 23.33万 - 项目类别:
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