We are using various mouse models to study intestinal immune-microbes interaction in health and diseases such as IBD, aim to develop human personalized medicine. Our recent works demonstrated how pathogenic viruses, such as norovirus and rotavirus, are sensed by intestinal epithelial cells-specific Nod-like recpetors-Nlrp6 and Nlrp9, and how they mediate antivirus immune defense through divergent mechanisms (Nature, 2017; Science, 2015). Our work also illustrated how commensal viruses are sensed by Rig-I in intestinal dendritic cells, and how Rig-I/IRF1/IL-15 signaling maintained the expansion of intraepithelial lymphocytes (Nature Immunology, 2019). We also studied the roles of epigenetic regulators in T helper cells and cytokine secreted by T helper cells in intestinal inflammation and autoimmune diseases (Nature, 2017; Nature Communications, 2015; Nature Medicine, 2012; J Exp Med, 2010; J Immunol, 2010). These mechanisms of innate immune defense or T helper cell response characterized in the intestine, may provide useful targets for the manipulation of the immune responses to regulate intestinal inflammation.