Deciphering the role of IGF2BP3 in early life T cell development

解读 IGF2BP3 在生命早期 T 细胞发育中的作用

基本信息

批准号：
10038861
负责人：
Nitya Jain
金额：
$ 20.66万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-22 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10038861
关键词：
Adult Antibiotics Antigens Appearance Binding Binding Proteins Birth Bone Marrow Bone Marrow Cells CD8B1 gene Cells Chimera organism Complex Cytoplasmic Protein Development Discrimination Doctor of Philosophy Enterobacteria phage P1 Cre recombinase Environment Event Exposure to Expression Profiling Face Family Fetal Development Foundations Friends Gene Expression Gene Targeting Genes Genetic Goals Growth Hematopoiesis Hematopoietic Hematopoietic stem cells House mice Immune Immune response Immune system Immunity Infant Insulin-Like Growth Factor II Knockout Mice Life Light Lymphocyte Malignant Neoplasms Messenger RNA Mus Nature Neonatal Newborn Infant Nutrient Phenotype Placenta Process Proteins RNA RNA-Binding Proteins Reporter Reporting Residual state Role Spleen T cell regulation T-Cell Development T-Lymphocyte T-Lymphocyte Subsets Thymus Gland Time Translations Xenobiotics cell type experimental study fetal gut microbiota in utero interest microbial microorganism antigen mouse model novel postnatal precursor cell premature prevent programs promoter transcription factor transcriptome sequencing

项目摘要

PI/PD: Jain, Nitya Ph.D. PROJECT SUMMARY The immune system faces unique challenges in early life. In utero, the developing fetal immune system must tolerate myriad maternal antigenic exposures including nutrients and xenobiotics that are transferred across the placenta. At birth, the still developing immune system of the newborn is abruptly exposed to a multitude of environmental and microbial antigens and must rapidly form a discrimination of friend from foe. The early life immune system itself undergoes rapid and radical changes during this time that are driven by these antigenic events and the action of transcription factor regulatory circuits directing the development and effector programming of specific immune cell types. The period immediately after birth thus represents a unique immune state with significant overlap of fetal and postnatally derived immune cells. Thus, there is great interest in understanding the genetic program underlying these developmental transitions that determine quality of immune cells being generated over ontogeny. In preliminary experiments, a comparison of gene expression profiles of developing thymic cells from neonatal and adult mice by RNA-seq identified the gene Igf2bp3 to be highly expressed in early life. The goal of this R21 application is to explore the role of IGF2BP3 in early life T cell development. Using novel mouse models that we have generated, we will determine the precise expression of IGF2BP3 over ontogeny and the consequences of deletion of IGF2BP3 in thymic precursor cells on T cell development and function. These foundational studies will shed light on the makeup of the immune repertoire during the period of overlap of fetal and postnatal immune cells and strive to understand the nature of immune responses during this transitional period.

PI/PD：Jain、Nitya 博士项目概要免疫系统在生命早期面临着独特的挑战。在子宫内，发育中的胎儿免疫系统必须耐受无数母体抗原暴露，包括转移的营养物质和异生物质胎盘。出生时，新生儿仍在发育的免疫系统突然暴露于多种环境和微生物抗原，必须迅速形成朋友和敌人的区别。早年生活在此期间，免疫系统本身经历了由这些抗原驱动的快速而彻底的变化指导发育和效应器的转录因子调节回路的事件和作用特定免疫细胞类型的编程。因此，出生后的这段时期代表了一个独特的时期。胎儿和出生后衍生的免疫细胞显着重叠的免疫状态。因此，引起了极大的兴趣理解这些决定质量的发育转变背后的遗传程序免疫细胞在个体发育过程中产生。在初步实验中，比较了新生儿胸腺细胞发育的基因表达谱通过 RNA-seq 鉴定成年小鼠的 Igf2bp3 基因在生命早期高度表达。 R21的目标该应用的目的是探索IGF2BP3在生命早期T细胞发育中的作用。使用新颖的小鼠模型我们已经生成了，我们将确定 IGF2BP3 在个体发育上的精确表达以及胸腺前体细胞中 IGF2BP3 缺失对 T 细胞发育和功能的影响。这些基础研究将揭示胎儿重叠期间免疫库的构成和出生后免疫细胞，并努力了解这一过渡期间免疫反应的本质时期。