Trends Immunol. 2025 Nov 19:S1471-4906(25)00253-4. doi: 10.1016/j.it.2025.10.009. Online ahead of print.

ABSTRACT

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.

PMID:41266201 | DOI:10.1016/j.it.2025.10.009