Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis

Arthritis Rheum. 2009 Apr;60(4):955-65. doi: 10.1002/art.24389.


Objective: Subclinical gut inflammation is common in spondylarthritis, but the immunologic abnormalities underlying this process are undefined. Perturbation of the interleukin-23 (IL-23)/Th17 axis has emerged as a fundamental trigger of chronic inflammation. This study was undertaken to investigate the expression and tissue distribution of IL-23/Th17-related molecules in Crohn's disease (CD) and in subclinical gut inflammation in ankylosing spondylitis (AS).

Methods: Quantitative gene expression analysis of Th1/Th2 and IL-23/Th17 responses was performed in intestinal biopsy samples obtained from 12 patients with CD, 15 patients with AS, and 13 controls. IL-23 tissue distribution and identification of IL-23-producing cells were evaluated by immunohistochemistry.

Results: We demonstrated a strong and significant up-regulation of IL-23p19 transcripts in the terminal ileum in patients with AS and patients with CD. IL-23 was abundantly produced by infiltrating monocyte-like cells in inflamed mucosa from AS and CD patients. Notably, we also identified Paneth cells as a major source of IL-23 in patients with AS, patients with CD, and normal controls. Unlike CD, in AS patients, IL-23 was not associated with up-regulation of IL-17 and the IL-17-inducing cytokines IL-6 and IL-1beta. Finally, while the Th1-related cytokines interferon-gamma, IL-12p35, and IL-27p28 were overexpressed only in CD patients, IL-4, IL-5, and STAT-6 were also significantly increased in AS patients.

Conclusion: Our findings indicate that overexpression of IL-23, but not IL-17, is a pivotal feature of subclinical gut inflammation in AS. Identification of resident Paneth cells as a pivotal source of IL-23 in physiologic and pathologic conditions strongly suggests that IL-23 is a master regulator of gut mucosal immunity, providing a pathophysiologic significance to the reported association between IL-23 receptor polymorphisms and intestinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Expression / immunology
  • Humans
  • Ileitis / epidemiology
  • Ileitis / immunology*
  • Ileitis / physiopathology
  • Ileum / immunology
  • Ileum / metabolism
  • Interleukin-17 / genetics*
  • Interleukin-17 / metabolism
  • Interleukin-23 Subunit p19 / genetics*
  • Interleukin-23 Subunit p19 / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Paneth Cells / immunology
  • Paneth Cells / metabolism
  • Prevalence
  • RNA, Messenger / metabolism
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Spondylitis, Ankylosing / epidemiology
  • Spondylitis, Ankylosing / immunology*
  • Spondylitis, Ankylosing / physiopathology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Up-Regulation / immunology


  • IL23A protein, human
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT1 protein, human