Figure 5.

Importance of IL-18 for gut homeostasis. Intestinal epithelial cells utilize various inflammasomes for the constitutive production of IL-18. Under SPF conditions, colonic epithelial cells release IL-18 dependent on the NLRP6 inflammasome, which in turn activates epithelial cells to produce antimicrobial peptides (AMPs) to maintain microbiome homeostasis. Nlrp6^−/− mice spontaneously develop dysbiosis resulting in colitis. The NLRP6 inflammasome is involved in the generation of the homeostatic mucin layer by intestinal epithelial cells. IL-18 derived from pyrin inflammasome activation is involved in gut homeostasis through the generation of intact tight junction (Tj) formation. Furthermore, pyrin inflammation-mediated IL-18 protects against colitis-associated colorectal cancer by reducing the stemness of colon epithelial cells.