This is consistent with prior studies of the absence of microbial invasion of the mucus layers in the context of reduced IgA.34,35 RAG1−/− or immunodeficient mice are known to have a more robust innate immune response to colonization with microbes.36–38 Thus, TRAG mice might develop colitis because the RAG1−/− immune system is primed to a more robust immune response to microbes and expression of TNFAIP3 in the epithelium facilitates microbial invasion. This evidence concerns the gene RAG1 and colitis.