Transcriptional Regulation of CD4+ T Cell Differentiation and Diversified Memory
CD4 T 细胞分化和多样化记忆的转录调控
基本信息
- 批准号:10714458
- 负责人:
- 金额:$ 50.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-07 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAutoimmune DiseasesB-LymphocytesBACH2 geneBLR1 geneBiological ModelsCD4 Positive T LymphocytesCell Differentiation processCellsChromatinCommunicable DiseasesComplexDataDevelopmentGenerationsGenesGoalsHelper-Inducer T-LymphocyteHumoral ImmunitiesIL2RA geneImmune responseImmunizationInflammatoryInterleukin-6KnowledgeMaintenanceMapsMemoryModelingMolecularMusPathway interactionsPopulationPositioning AttributeProcessProteinsRegulationReporterResearchRoleStructure of germinal center of lymph nodeT cell differentiationT cell responseT memory cellT-Lymphocyte SubsetsTranscriptional RegulationVaccinesWorkarmcytokinecytotoxicdesigninfectious disease treatmentintraperitonealmemory CD4 T lymphocytemouse modelnew pandemicnovelnovel markerpandemic potentialpandemic responseprogrammed cell death protein 1public health relevancereceptorresponsesingle-cell RNA sequencingtranscription factortranscriptometranscriptome sequencingvaccine developmentvaccine strategy
项目摘要
Project Summary
T follicular helper (Tfh) cells are essential for germinal center (GC) responses and long-term
humoral immunity. However, the complex regulation that determines the differentiation of Tfh cells, in
particular, the initial CXCR5– versus CXCR5+ CD4+ T cell differentiation, the developmental progression
of CXCR5+CD4+ T cells to become GC-Tfh cells, and the generation of follicular helper-like memory
CD4+ T cells expressing CXCR5, are still not fully understood. Our proposal aims to fill in these
knowledge gaps with long-term goals to identify novel genes/pathways underlying the CD4+ T cell
differentiation.
In our preliminary studies, we have discovered a novel network engaging various
factors/pathways that fine-tunes CXCR5+ versus CXCR5– CD4+ T cell differentiation and regulates the
generation of cytotoxic CD4+ T cells in the early stage of CD4+ T cell response. By combining RNA-seq,
ATAC-seq, and single cell RNA-seq, our preliminary data also suggest that the PD-1+CXCR5+ pre-Tfh
cells undergo substantial further differentiation to become PD-1hiCXCR5hi GC-Tfh cells. Additionally, we
have generated novel “fate-mapping” reporter mice that will allow us to track the varied CXCR5– and
CXCR5+ memory CD4+ T cells. Thus, in this application, we aim to dissect the molecular underpinning
of the early stage CXCR5+ versus CXCR5– CD4+ T cell differentiation as well as to elucidate the
mechanisms underlying the pre- to GC-Tfh differentiation and the generation of diversified CD4+ T cell
memory.
Our work will have a profound impact on the field of CD4+ T cell differentiation. The research will
not only shed new light on our understanding of the mechanisms underlying the multiple steps of Tfh
cell differentiation but also establish new model systems for memory CD4+ T cell studies. This proposal
has the potential to provide important knowledge on how to control both the humoral and the cellular
arms of the CD4+ T cell response to aid vaccine development for new pandemic threats and help the
treatment of infectious diseases and autoimmune disorders.
项目摘要
滤泡辅助性T细胞(Tfh)对于生殖中心(GC)反应和长期免疫应答是必不可少的。
体液免疫然而,决定Tfh细胞分化的复杂调控,
特别是,初始CXCR 5-与CXCR 5 + CD 4 + T细胞分化,发育进程,
CXCR 5 + CD 4 + T细胞成为GC-Tfh细胞,并产生滤泡辅助样记忆
表达CXCR 5的CD 4 + T细胞仍然没有完全了解。我们的建议旨在填补这些
长期目标的知识差距,以确定新的基因/途径的CD 4 + T细胞
分化
在我们的初步研究中,我们发现了一个新的网络,
微调CXCR 5+与CXCR 5-CD 4 + T细胞分化的因子/途径,
在CD 4 + T细胞应答的早期阶段产生细胞毒性CD 4 + T细胞。通过结合RNA-seq,
ATAC-seq和单细胞RNA-seq,我们的初步数据也表明PD-1+ CXCR 5+前Tfh
细胞经历实质上的进一步分化以成为PD-1hiCXCR 5 hi GC-Tfh细胞。另外我们
已经产生了新的“命运映射”报告小鼠,这将使我们能够跟踪不同的CXCR 5-和
CXCR 5+记忆性CD 4 + T细胞。因此,在本申请中,我们的目标是剖析分子基础
早期CXCR 5+与CXCR 5-CD 4 + T细胞分化的关系,以及阐明
GC-Tfh前分化和多样化CD 4 + T细胞产生的机制
记忆
我们的工作将对CD 4 + T细胞分化领域产生深远的影响。这项研究将
不仅为我们理解Tfh多步骤的机制提供了新的线索,
细胞分化,而且还建立了新的模型系统的记忆CD 4 + T细胞的研究。这项建议
有可能提供关于如何控制体液和细胞免疫的重要知识。
CD 4 + T细胞反应的武器,以帮助疫苗开发新的大流行威胁,并帮助
治疗感染性疾病和自身免疫性疾病。
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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Hui Hu的其他文献
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{{ truncateString('Hui Hu', 18)}}的其他基金
Transcriptional Regulation of CD4+ T Cell Differentiation and Diversified Memory
CD4 T 细胞分化和多样化记忆的转录调控
- 批准号:
10741301 - 财政年份:2022
- 资助金额:
$ 50.79万 - 项目类别:
Hypertensive Disorders of Pregnancy and Early Risk of Maternal CVD: Influence of the External Exposome
妊娠期高血压疾病和孕产妇心血管疾病的早期风险:外部暴露的影响
- 批准号:
10645046 - 财政年份:2021
- 资助金额:
$ 50.79万 - 项目类别:
Hypertensive Disorders of Pregnancy and Early Risk of Maternal CVD: Influence of the External Exposome
妊娠期高血压疾病和孕产妇心血管疾病的早期风险:外部暴露的影响
- 批准号:
10523580 - 财政年份:2021
- 资助金额:
$ 50.79万 - 项目类别:
Hypertensive Disorders of Pregnancy and Early Risk of Maternal CVD: Influence of the External Exposome
妊娠期高血压疾病和孕产妇心血管疾病的早期风险:外部暴露的影响
- 批准号:
10214088 - 财政年份:2021
- 资助金额:
$ 50.79万 - 项目类别:
Hypertensive Disorders of Pregnancy and Early Risk of Maternal CVD: Influence of the External Exposome
妊娠期高血压疾病和孕产妇心血管疾病的早期风险:外部暴露的影响
- 批准号:
10414064 - 财政年份:2021
- 资助金额:
$ 50.79万 - 项目类别:
Hypertensive Disorders of Pregnancy and Early Risk of Maternal CVD: Influence of the External Exposome
妊娠期高血压疾病和孕产妇心血管疾病的早期风险:外部暴露的影响
- 批准号:
10771766 - 财政年份:2021
- 资助金额:
$ 50.79万 - 项目类别:
Regulation of Tfh cell differentiation and humoral immunity
Tfh细胞分化和体液免疫的调节
- 批准号:
10165471 - 财政年份:2017
- 资助金额:
$ 50.79万 - 项目类别:
Transcriptional regulation of T cell quiescience and activation
T 细胞静止和激活的转录调控
- 批准号:
8872018 - 财政年份:2012
- 资助金额:
$ 50.79万 - 项目类别:
Negative regulatory pathways in T cell quiescence and T cell response
T 细胞静止和 T 细胞反应中的负调控途径
- 批准号:
8549950 - 财政年份:2012
- 资助金额:
$ 50.79万 - 项目类别:
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