IL-22 signaling is known to induce the production of nucleotide oligomerization domain-containing protein 2 (NOD2), which is related to the regulation of innate immune response and microbial recognition.58 Furthermore, NOD2 is one of the most widely implicated genes in the etiology of Crohn’s disease.59 We here demonstrated that Mgat5−/− mice also exhibited a significant downregulation of Nod2 (Figure 3(n)), reinforcing the negative impact of the impaired IL-22 signaling (either by decreased IL-22-derived ILC3 or increased Il22ra2) in the homeostatic gut environment. This evidence concerns the gene IL22 and Crohn disease.