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

淋巴结节是能够有效启动适应性免疫反应的中枢，为相应的组织量身定做，如皮肤、肠道或肺。淋巴结间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，肠道引流的淋巴结基质细胞被证明可以促进耐受性免疫反应，即通过高诱导调节性T细胞来促进免疫反应。在这里，我们的目标是识别表观遗传修饰的基因位点，这些基因位点转化为淋巴结基质细胞中组织定位和共生特异性的转录活性。综合分析单细胞和常规群体转录，以及不同淋巴结基质细胞的全基因组CpG甲基化和DNA可及性，我们将能够：1)剖析不同淋巴结基质细胞对免疫调节功能的贡献；2)确定易受环境因素影响的基因调控网络；3)确定定义不同淋巴结功能特性的表观遗传和转录网络。更好地了解调控淋巴结基质细胞诱导调节性T细胞能力的潜在基因调控网络，将使我们能够利用淋巴结基质细胞的耐受潜力来改善肠道炎性疾病。

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.