Epigenetic imprinting of location- and commensal-dependent immunomodulatory properties in mesenteric lymph node stromal cells

肠系膜淋巴结基质细胞位置和共生依赖性免疫调节特性的表观遗传印记

• 批准号: 397151636
• 负责人: Dr. Jörn Pezoldt
• 金额: --
• 依托单位: Laboratory of Systems Biology and Genetics(LSBG)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/397151636?language=en
• 关键词: Epigenetic; imprinting; location; commensal; dependent

Lymph nodes are the hubs to enable effective initiation of adaptive immune responses, tailored to the respective tissue, such as skin, intestine or lung. Lymph node stromal cells are the permanent infrastructural component and also contribute to shape tissue-specific immune responses. Particularly, the gut-draining lymph node stromal cells have been shown to promote tolerogenic immune responses, namely by contributing to high induction of regulatory T cells.Here, we aim to identify epigenetically modified gene loci, which translate into tissue location- and commensal-specific transcriptional activity in lymph node stromal cells. Integrative analysis of single-cell and conventional population transcriptomics together with genome-wide CpG methylation and DNA accessibility obtained for different lymph node stromal cells will allow us to:1) Dissect the contribution of different lymph node stromal cells to immunomodulatory function.2) Identify gene regulatory networks susceptible to environmental cues.3) Determine the epigenetic and transcriptional networks that define the functional properties of different lymph nodes.A better understanding into the underlying gene regulatory networks that govern the capacity of lymph node stromal cells to promote induction of regulatory T cells, could allow us to leverage the tolerogenic potential of lymph node stromal cells to ameliorate intestinal inflammatory disorders.

淋巴结是能够有效启动适应性免疫应答的枢纽，适应于相应的组织，如皮肤、肠或肺。淋巴结基质细胞是永久性的基础结构成分，也有助于形成组织特异性免疫反应。特别是，肠道引流淋巴结基质细胞已被证明可以促进致耐受性免疫应答，即通过促进调节性T细胞的高诱导，我们的目标是确定表观遗传修饰的基因位点，这些基因位点在淋巴结基质细胞中转化为组织位置和组织特异性转录活性。单细胞和常规群体转录组学的综合分析以及针对不同淋巴结基质细胞获得的全基因组CpG甲基化和DNA可及性将使我们能够：1） 解剖不同淋巴结基质细胞对免疫调节功能的贡献。2） 识别易受环境线索影响的基因调控网络。 确定定义不同淋巴结功能特性的表观遗传和转录网络，更好地了解控制淋巴结基质细胞促进调节性T细胞诱导能力的潜在基因调控网络，可以使我们能够利用淋巴结基质细胞的耐受性潜力来改善肠道炎症性疾病。