Consistent with this, intestinal organoids double deficient for Atg16l1 and Ormdl3, another ER stress regulatory gene, genetic variants of which confer genetic risk for IBD (McGovern et al., 2010), also exhibited significant up-regulation of ISG genes and Tnf induction in response to IL-22 stimulation (Fig. S4 C). Here, ATG16L1 is linked to inflammatory bowel disease.