Establishing The Immune Potential Of Enteric Glial Cells

建立肠胶质细胞的免疫潜能

• 批准号: EP/Y036840/1
• 负责人: Vassilis Pachnis
• 金额: $ 25.55万
• 依托单位: The Francis Crick Institute
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY036840%2F1
• 关键词: Establishing; Immune; Potential; Enteric; Glial

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.

肠神经胶质细胞（EGC）对于维持神经元存活和肠神经系统功能至关重要。除了为神经元提供支持外，新的证据表明 EGC 对于调节肠道免疫功能和组织稳态也至关重要。事实上，来自不同系统的越来越多的证据表明，免疫活性和宿主防御不仅是造血谱系的责任，而且其他几种细胞类型也参与免疫反应。这种“非专业”免疫细胞被认为在稳定状态下具有“免疫潜力”，这表明它们已经准备好对预期刺激做出反应。尽管人们对 EGC 的免疫调节功能越来越感兴趣，但其免疫潜力的分子基础仍然难以捉摸。拟议的工作将定义 EGC 免疫功能的发育起始并解决支撑其的因素。具体来说，我们将使用多组学（转录组和表观基因组）分析来鉴定 EGC 在体内表达的一组免疫相关基因，并在单细胞水平上确定它们的染色质可及性。转录组和表观基因组特征将被策划并用于进一步定义 EGC 体内免疫潜力的发育起始。为了确定 EGC 免疫潜力发展所涉及的环境因素和分子级联反应，我们将评估微生物群和 IFNg 信号传导的作用。该项目将探索神经科学、神经发育和免疫学兴趣中心的新问题，填补当前知识的重大空白。此外，我们的工作将生成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 EGC 免疫潜力的发展可能为利用 EGC 作为肠道免疫失调相关疾病的治疗靶点铺平道路。