The interleukin-23 axis in intestinal inflammation

Immunol Rev. 2008 Dec:226:147-59. doi: 10.1111/j.1600-065X.2008.00705.x.

Abstract

Immune responses in the intestine are tightly regulated to ensure host protective immunity in the absence of immune pathology. Interleukin-23 (IL-23) has recently been shown to be a key player in influencing the balance between tolerance and immunity in the intestine. Production of IL-23 is enriched within the intestine and has been shown to orchestrate T-cell-dependent and T-cell-independent pathways of intestinal inflammation through effects on T-helper 1 (Th1) and Th17-associated cytokines. Furthermore, IL-23 restrains regulatory T-cell responses in the gut, favoring inflammation. Polymorphisms in the IL-23 receptor have been associated with susceptibility to inflammatory bowel diseases (IBDs) in humans, pinpointing the IL-23 axis as a key, conserved pathway in intestinal homeostasis. In addition to its role in dysregulated inflammatory responses, there is also evidence that IL-23 and the Th17 axis mediate beneficial roles in host protective immunity and barrier function in the intestine. Here we discuss the dual roles of IL-23 in intestinal immunity and how IL-23 and downstream effector pathways may make novel targets for the treatment of IBD.

Publication types

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

MeSH terms

  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-23 / immunology*
  • Interleukin-23 / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Signal Transduction / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Interleukin-17
  • Interleukin-23