Interleukin-22: the hub bridging gut homeostasis and metabolism

Trends Immunol. 2026 Feb;47(2):147-159. doi: 10.1016/j.it.2025.10.009. Epub 2025 Nov 20.

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.

Keywords: epithelial barrier; inflammatory bowel disease; intestinal metabolism; metabolic disorders; mucosal immunity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gastrointestinal Microbiome
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Immunity, Mucosal
  • Inflammatory Bowel Diseases* / immunology
  • Inflammatory Bowel Diseases* / metabolism
  • Interleukin-22
  • Interleukins* / immunology
  • Interleukins* / metabolism
  • Intestinal Mucosa* / immunology
  • Intestinal Mucosa* / metabolism
  • Mice

Substances

  • Interleukin-22
  • Interleukins