Establishing The Immune Potential Of Enteric Glial Cells

肠神经胶质细胞（EGCs）对维持肠神经系统的神经存活和功能至关重要。除了为神经元提供支持外，新出现的证据表明，EGCs对肠道免疫功能和组织稳态的调节也至关重要。事实上，越来越多来自不同系统的证据表明，免疫活性和宿主防御不仅仅是造血系的责任，还有其他几种细胞类型参与免疫反应。这种“非专业”免疫细胞被认为在稳定状态下具有“免疫潜能”，这表明它们已经准备好对预期刺激作出反应。尽管人们对EGCs的免疫调节功能越来越感兴趣，但其免疫潜能的分子基础仍然难以捉摸。建议的工作将确定EGC免疫功能的发育开始，并解决支持它的因素。具体来说，我们将利用多组学（转录组学和表观基因组学）分析，确定EGCs在体内表达的一组免疫相关基因，并在单细胞水平上建立它们的染色质可及性。转录组学和表观基因组学特征将被整理并用于进一步定义EGC体内免疫潜能的发育性发病。为了确定与EGCs免疫潜能发展相关的环境因素和分子级联反应，我们将评估微生物群和IFNg信号的作用。该项目将探索神经科学、神经发育和免疫学领域的新问题，填补当前知识的重大空白。此外，我们的工作将产生一系列开放获取的数据集，这将有利于许多未来的研究。最终，表征EGCs免疫潜能的发展可以为利用EGCs作为与肠道免疫失调相关的治疗靶点铺平道路。

Enteric glia cells (EGCs) are vital for maintaining neuronal survival and functions of the enteric nervous system. Besides providing support to neurons, emerging evidence suggests that EGCs are also critical for the regulation of intestinal immune functions and tissue homeostasis. Indeed, increasing evidence from different systems indicates that immune activity and host defense is not only the responsibility of the hematopoietic lineage and that several other cell types partake in immune responses. Such "non-professional" immune cells are thought to possess "immune potential" at steady state, suggesting that they are already primed to react to a prospective stimulus. Despite the growing interest in the immune-regulatory function of EGCs, the molecular basis of their immune potential remains elusive. The proposed work will define the developmental onset of the EGC immune function and address the factors that underpin it. Specifically, we will identify the set of immune-related genes expressed by EGCs in vivo and establish their chromatin accessibility at the single cell level, using multiomic (transcriptomic and epigenomic) profiling. Transcriptomic and epigenomic signatures will be curated and used to further define the developmental onset of EGC immune potential in vivo. To identify environmental factors and molecular cascades implicated in the development of the immune potential of EGCs, we will evaluate the role of microbiota and IFNg signaling. The proposed project will explore novel questions, lying in the center of interest of neuroscience, neurodevelopment and immunology, filling a significant gap in the current knowledge. In addition, our work will generate a series of open-access datasets that will benefit numerous future studies. Ultimately, characterizing the development of EGCs immune potential could pave inroads for harnessing EGCs as therapeutic target in conditions associated with immune dysregulation of the intestine.