Evaluating Reactive Enteric Glia-Derived Cytokine’s Effect on Neuroinflammation and Enteric Neuron Viability
Tommy Luong
Department of Biology
Faculty Supervisor: Lily Chen
Neuroinflammation of the gastrointestinal (GI) tract has been associated with gastrointestinal and neurological diseases, such as Inflammatory Bowel Disease (IBD) and Parkinson’s Disease. Enteric glia, supporting cells in the GI tract’s enteric nervous system (ENS), are critical in responding to inflammation in these diseases. However, enteric glia becomes reactive during neuroinflammation, causing nearby neurons and ENS cells to become injured or die. Furthermore, challenges in harvesting, culturing, and manipulating enteric neurons and glia from primary tissue have limited understanding of reactive gliosis in the ENS. To overcome these challenges, we developed a human pluripotent stem cell (hPSC) differentiation protocol for enteric neurons and glia. Using lipopolysaccharide (LPS) treatment to model neuroinflammation, we discovered that LPS-treated enteric glia secretes factors that induce functional changes in enteric neurons, leading to neuronal apoptosis. Our preliminary data suggested that four cytokines—IL6, CXCL1, CCL2, and CXCL12—are secreted by LPS-treated enteric glia. Utilizing CRISPR-Cas9, we genetically knocked out these four cytokines in enteric glia to evaluate their effects on enteric neuron viability and neuroinflammation.