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

• 批准号: 10199972
• 负责人: Nitya Jain
• 金额: $ 24.86万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-22 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10199972
• 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; 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

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 项目摘要 免疫系统在生命早期面临独特的挑战。在子宫内，发育中的胎儿免疫系统必须 耐受无数的母体抗原暴露，包括营养素和外源性物质， 胎盘在出生时，新生儿仍在发育的免疫系统突然暴露于大量的 环境和微生物抗原，必须迅速形成敌友的区别。早期生活 在此期间，免疫系统自身经历了由这些抗原驱动快速和根本的变化， 事件和转录因子调控电路的作用，指导发展和效应 编程特定的免疫细胞类型。因此，出生后的这段时间代表了一个独特的 具有胎儿和出生后衍生的免疫细胞显著重叠的免疫状态。因此， 在理解这些决定发育质量的发育转变背后的遗传程序时， 在个体发育过程中产生的免疫细胞。 在初步实验中，比较了新生儿胸腺细胞发育过程中的基因表达谱， 成年小鼠通过RNA-seq鉴定出Igf 2bp 3基因在生命早期高度表达。R21的目标是 本申请的目的是探索IGF 2BP 3在早期生命T细胞发育中的作用。使用新的小鼠模型， 我们已经产生了，我们将确定IGF 2BP 3在个体发育中的精确表达， 胸腺前体细胞中IGF 2BP 3缺失对T细胞发育和功能的影响。这些 基础研究将阐明胎儿免疫重叠期间免疫库的组成， 和出生后的免疫细胞，并努力了解免疫反应的性质，在这一过渡 期

项目成果

RXRα Regulates the Development of Resident Tissue Macrophages.

• DOI: 10.4049/immunohorizons.2200019
• 发表时间: 2022-06-22
• 期刊: ImmunoHorizons
• 作者: Philpott, Jordan;Kazimierczyk, Simon;Korgaonkar, Parimal;Bordt, Evan;Zois, Jaclyn;Vasudevan, Chithirachelvi;Meng, Di;Bhatia, Ishan;Lu, Naifang;Jimena, Brittany;Porter, Caryn;Cherayil, Bobby J;Jain, Nitya
• 通讯作者: Jain, Nitya