In conclusion, we demonstrate that IEC-specific TRIM29 deficiency controls infections by enteric RNA viruses by targeting NLRP6 and NLRP9b for degradation to enhance IFN-λ3 and IL-18 production in IECs and augment the recruitment of protective intraepithelial Ly6A+CCR9+CD4+ T cells in small intestines. Here, NLRP6 is linked to infection.