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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 phd。