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 Ph.D. 项目摘要 免疫系统在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 耐受的无数母性抗原暴露，包括养分和异生物学 胎盘。出生时，仍在发展的新生儿免疫系统突然暴露于许多 环境和微生物抗原，必须迅速形成与敌人的朋友的歧视。早期生活 在这段时间内，免疫系统本身经历了快速而根本的变化，这些变化是由这些抗原驱动的 事件和转录因子调节电路的作用指导开发和效应器 特定免疫细胞类型的编程。因此，出生后立即的时期代表了一个独特的时期 免疫状态具有显着的胎儿和产后衍生的免疫细胞的重叠。因此，有极大的兴趣 在理解这些发展过渡的基础基础的基因计划时 免疫细胞是在个体发育中产生的。 在初步实验中，比较了新生儿发育中的胸腺细胞的基因表达谱 RNA-seq的成年小鼠鉴定出在早期生命中高度表达基因IGF2BP3。 R21的目标 应用是探讨IGF2BP3在早期生命T细胞发育中的作用。使用新颖的鼠标模型 我们已经产生了，我们将确定IGF2BP3的精确表达在本体发育和 胸腺前体细胞中IGF2BP3缺失对T细胞发育和功能的后果。这些 基础研究将阐明胎儿重叠期间免疫库的构成 和产后免疫细胞，并努力理解这种过渡期间免疫反应的性质 时期。

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