Il22ra1, the interleukin 22 receptor subunit alpha 1, is a key component in the interleukin-22 (IL-22) signaling pathway. IL-22/IL22RA1 signaling is involved in various biological processes such as immunity, tissue homeostasis, and lipid and glucose metabolism [1-6]. It is associated with the JAK/STAT pathway, which is crucial in tumor progression and other cellular functions [2].

In multiple studies using gene knockout models, significant insights have been gained. Hepatocyte-specific Il22ra1 knockout mice show diet-induced hepatic steatosis, insulin resistance, and other metabolic disorders due to increased lipogenesis mediated by oxysterol accumulation [1]. In pancreatic cancer, IL22RA1hi cells have higher stemness and tumorigenicity, and IL22 promotes pancreatic cancer stemness via IL22RA1/STAT3 signaling [3]. In the intestine, using IEC type-specific Il22ra1 conditional knockout mice, IL-22Ra1 signaling in MATH1+ cells is essential for mucosal barrier maintenance and tissue regeneration [4]. Also, intestinal epithelium-specific Il22ra1 knockout mice help elucidate the role of intestinal IL-22RA1 signaling in regulating systemic obesity-associated disorders [5].

In conclusion, Il22ra1 plays a vital role in maintaining normal physiological functions such as lipid and glucose metabolism, mucosal barrier protection, and tissue regeneration. Its dysregulation is associated with diseases including non-alcoholic fatty liver disease (NAFLD), pancreatic cancer, and obesity-associated disorders. The use of Il22ra1 knockout and conditional knockout mouse models has been instrumental in uncovering these disease-related mechanisms, providing potential therapeutic targets for these conditions.