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

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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.