The colonic gene expression levels of several other inflammatory mediators implicated in regulating intestinal inflammation and/or obesity and metabolic disease, including Il1b, Tnfa, Il6, Il10 and Ifng, were similar between wt and Il36rn−/− mice (Supplementary Fig. 3a), indicating that loss of IL-36Ra expression did not lead to a broad non-specific state of inflammation in the gut. Here, IL6 is linked to obesity due to melanocortin 4 receptor deficiency.