Deciphering the role of IGF2BP3 in early life T cell development

PI/PD：Jain，Nitya博士 项目总结 免疫系统在早期生命中面临着独特的挑战。在子宫内，发育中的胎儿免疫系统必须 耐受无数的母体抗原暴露，包括营养物质和外源物质 胎盘。在出生时，新生儿仍在发育中的免疫系统突然暴露在大量 环境和微生物抗原，必须迅速形成敌友区别。早期的生活 免疫系统本身在这段时间内经历了快速和彻底的变化，这些变化是由这些抗原驱动的 指导发育和效应器的转录因子调节电路的事件和作用 特定免疫细胞类型的编程。因此，出生后紧随其后的时期代表着一种独特的 胎儿免疫细胞和出生后免疫细胞明显重叠的免疫状态。因此，人们对此非常感兴趣 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免疫细胞。 在初步实验中，比较了发育中的新生儿胸腺细胞的基因表达谱 成年小鼠通过RNA-SEQ鉴定出Igf2bp3基因在生命早期高表达。这款R21的目标是 应用目的是探讨IGF2BP3在生命早期T细胞发育中的作用。使用新的鼠标模型， 我们已经生成了IGF2BP3，我们将确定IGF2BP3在个体发育和 胸腺前体细胞IGF2BP3缺失对T细胞发育和功能的影响这些 基础性研究将阐明胎儿重叠时期免疫系统的组成 和出生后免疫细胞，并努力了解在这一过渡期间的免疫反应的性质 句号。

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.