Regulation of Enteric Nervous System Function by Group 3 Innate Lymphoid Cells

项目总结 肠道神经系统(Ens)是控制肠道蠕动和营养等关键功能的关键。 吸收。新兴的范式表明，神经元和免疫细胞之间的相互作用从根本上说 周围组织中的冲击性免疫和炎症。最近，有研究表明，ENS可以作用于 肠道免疫系统调节先天淋巴样细胞(ILCs)的功能。然而，尽管如此， 随着研究的进展，ILCs在ENS功能中的作用仍未被研究。在我的初步研究中，我定义了ILC 从基因上准备好与ENS相互作用，并支持它们的发育或功能。通过检查特定的 由ILC产生的因子，我定义了它是如何被调节的，并开发了一种特定于家族的基因敲除来证明 这条通路在增强ENS方面起着作用。本提案的目标是，在目标1中，利用体内和外部 活体模型，以确定调节ILC和相关因素的分子机制，在目标2中， 确定ILC衍生因子影响ENS的细胞机制及其重要性 炎症期间维持内毒素内环境平衡的相互作用。总的来说，这两个目标将批判性地定义 ILCs在肠道健康和疾病状态下影响ENS功能的新分子机制， 这可能会引发新的预防、治疗或治疗策略。此外，它还将创造一个杰出的 为我在科学上的持续发展提供培训机会，并最终过渡为独立的 学术研究人员。

PROJECT SUMMARY The enteric nervous system (ENS) is critical for controlling key intestinal functions such as peristalsis and nutrient absorption. Emerging paradigms indicate that interactions between neurons and immune cells fundamentally impact immunity and inflammation in peripheral tissues. Recently, it has been shown that the ENS can act on the intestinal immune system to modify the function of innate lymphoid cells (ILCs). However, despite these advances, the role of ILCs in ENS function remains unexplored. In my preliminary studies, I defined that ILCs are genetically poised to interact with the ENS and support their development or function. By examining a specific factor produce by ILCs, I defined how it is regulated and developed a lineage-specific knockout to demonstrate this pathway plays a role in augmenting the ENS. To goals of this proposal are, in Aim 1, to utilize in vivo and ex vivo models to determine the molecular mechanisms that regulate ILCs and associated factors, and, in Aim 2, to determine the cellular mechanisms by which ILC-derived factors impacts the ENS and the importance of this interaction in maintaining ENS homeostasis during inflammation. Collectively, these two aims will critically define a novel molecular mechanism by which ILCs impact ENS function in states of intestinal health and disease, which could provoke novel preventative, therapeutic or curative strategies. Further, it will create an outstanding training opportunity for my continued development in science and eventual transition to become an independent academic researcher.