Importantly, the IL22 receptor is exclusively expressed by epithelial cells in the gut, and in IBD, there is an especially compelling case to probe interactions between IL22 and the colonic epithelium, since the colon is exclusively affected in UC and affects most patients with CD.1 In this study, we have exploited colonic epithelial organoids, in vivo disease models and tissue transcriptomics in a large datasets of CD patients with active colitis to probe IL22-colonic epithelial interactions and provide mechanistic insights into this critical dialogue. Here, IL22 is linked to colitis.