权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Genetic dissection of Id3-mediated pathways in gamma/delta lineage development

γ/δ谱系发育中Id3介导的途径的遗传解析

基本信息

批准号：
8608277
负责人：
Yuan Zhuang
金额：
$ 49.89万
依托单位：
RESEARCH INST OF FOX CHASE CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-15 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8608277
关键词：
Alleles Antigens Cell Lineage Cells Clonal Expansion Collaborations Complex DNA Sequence Rearrangement Development Dissection E protein Feedback Gene Dosage Gene Expression Gene Rearrangement Generations Genes Genetic Genetic Transcription Immune Immune response Immune system Immunotherapy Individual Infection Control Instruction Knock-out Knockout Mice Life Link Lymphocyte Maintenance Mediating Molecular Mus Natural regeneration Neonatal Nuclear Protein Outcome Outcome Study Pathway interactions Peripheral Play Production Program Research Project Grants Protein Family Regulation Reporter Role Signal Transduction Stable Populations Staging Subgroup System T-Cell Development T-Lymphocyte TCF3 gene Testing Thymus Gland Time Tissues Vent base chemokine clinical application cytokine fetal functional group genetic analysis helix-loop-helix protein differentiation inhibitor innate immune function mutant neoplastic cell pathogen postnatal progenitor protein function response self-renewal tool transcription factor transcriptome sequencing

项目摘要

γδ T cells represent a unique group of lymphocytes arising from the same thymic progenitors that also produce αβ T cells. Although these two groups of T cells are closely linked in development, they clearly play distinct roles in the immune system. In contrast to αβ T cells, which require help from innate immune cells, many γδ T cells appear to function as the first line of defense and can provide immediate responses to pathogens by secreting cytokines and chemokines. In this regard, γδ T cells perform important innate immune functions to help control infections and to facilitate the induction of adaptive immune responses. Thus far we know little, about the regulatory mechanisms that control the developmental timing and effector fates of individual functional groups of γδ T cells. Id3, a small nuclear protein, has been shown to play differential roles in lineage differentiation among different groups of γδ T cells. Id3 exerts its regulatory role by inhibiting the E-protein family of transcription factors, notably E2A and HEB, which directly regulate many lineage differentiation (c)vents including rearrangement and expression of the TCR γ and 5 genes. Although the importance of Id3 in regulating E-protein function during γδ lineage specification has been clearly established, the dynamic changes of downstream transcriptional networks are still poorly defined. We propose to use genetic means to distinguish the functions of Id3 at different stages and in different lineages of T cell development. In particular, the assessment of Id3-mediated pathways will be facilitated by genetic analysis involving the combination of conditional Id3, Id2, E2A, and HEB alleles. We will use this newly established genetic system to determine the mechanisms by which ld3 controls lineage choice between αβ and γδ T cell fate and lineage choice between different subtypes of γδ T cells. This genetic approach will be conducted in conjunction with the other three related projects included in this program project grant Together, we seek a comprehensive understanding of molecular pathways underlying γδ lineage choice and specification of effector function.

γδ T细胞是一种独特的淋巴细胞群，起源于相同的胸腺祖细胞