Our research seeks to understand the pathogenesis of inflammatory bowel disease, and understand interactions between host and the microbiome. In particular, we study the roles of dendritic cells. Dendritic cells are exquisitely sensitive to microbes, and after engaging microbes or microbial products, dendritic cells are reprogrammed into inflammatory cells with potent ability to activate other immune cells. Because of their potent influence over the immune system, dendritic cells are in a prime position to relay signals from the microbiome, and we have found that dendritic cells are key players in pathogenesis of inflammatory bowel disease. To prevent IBD, dendritic cells require the NF-kB suppressor, A20. A20 suppresses multiple disease-associated signaling pathways, including TNF, NOD2 and Toll-like receptors. Using biochemistry and in vivo analyses, we are interrogating the roles of these receptors and signaling pathways in regulating the responses of dendritic cells to the intestinal microbiome. Additionally, we seek to identify new signaling pathways by which DCs interact with microbial communities of the intestine.
