Modulating gut immunity: mechanisms of MHC-II upregulation in the absence of C3aR 4214

Abstract Description Within the gut, a localized complement system is critical in maintaining epithelial homeostasis, notably, the absence of the C3a receptor (C3aR) leads to heightened intestinal inflammation. Our preliminary findings suggest that the upregulation of Major Histocompatibility Complex-Class II (MHC-II) on intestinal epithelial cells (IEC) in our C3aRKO mice may be contributing to this increase in inflammation. To elucidate the potential molecular and microbial drivers of MHC-II upregulation in C3aR-deficient models, mice were treated with a cocktail treatment of antifungals and antibiotics to eliminate the native gut microbes. Flow Cytometry and Imaging Mass Cytometry methods were used to investigate baseline expression and confirmed our findings of increased MHC-ll expression in IECs isolated from our C3aRKO mouse model. We next utilized fecal microbiota transplant (FMT) to recapitulate our baseline results and determine if the effect was transferable from KO to WT mice. Metagenomic sequencing was performed on the FMT material and fecal samples taken post-FMT procedure to find potential microbial culprits. Additionally, RNA sequencing (RNA-seq) was performed on isolated IECs collected post-FMT to investigate intrinsic and differential gene changes. Taken in tandem, we report that the increase in expression is transferable, suggesting a microbial impact on expression, warranting further study into the impact of increased MHC-ll expression on intestinal inflammation and infection. Topic Categories Mucosal and Regional Immunology (MUC)