Establishing The Immune Potential Of Enteric Glial Cells

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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.