Promenakin

Excessive alcohol consumption drives the development of alcohol-associated liver disease (ALD), including steatohepatitis, cirrhosis, and hepatocellular carcinoma, and its associated complications, such as hepatorenal syndrome. Hepatocyte death, inflammation, and impaired liver regeneration are key processes implicated in the pathogenesis and progression of ALD. Despite extensive research, therapeutic options for ALD remain limited. IL-22 has emerged as a promising therapeutic target because of its hepatoprotective properties mediated through the activation of the STAT3 signaling pathway. IL-22 enhances hepatocyte survival by mitigating apoptosis, oxidative stress, and inflammation while simultaneously promoting liver regeneration through the proliferation of hepatocytes and hepatic progenitor cells and the up-regulation of growth factors. Additionally, IL-22 exerts protective effects on epithelial cells in various organs affected by ALD and its associated complications. Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration. However, the heterogeneity and multifactorial nature of ALD present ongoing challenges. Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits, and limitations.

IL-22, produced by various cell types including T helper (Th) 17 cells and group 3 innate lymphoid cells (ILC3s), plays a pivotal role in gut homeostasis by acting on non-hematopoietic cells. It promotes epithelial barrier integrity, tissue repair, and antimicrobial defense. Beyond its established function in mucosal immunity, emerging evidence reveals IL-22's involvement in regulating intestinal metabolism and protecting against systemic metabolic dysregulation. This review highlights recent advances in preclinical mouse models and human clinical data in IL-22 biology, focusing on its dual role in immune defense and metabolic control. Given the strong link between inflammatory bowel disease (IBD) and metabolic disorders, we further discuss IL-22's therapeutic potential in mitigating both intestinal inflammation and related metabolic complications.