Drs. Ciccia and Bombardieri contributed equally to this work.
Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis
Article first published online: 30 MAR 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 4, pages 955–965, April 2009
How to Cite
Ciccia, F., Bombardieri, M., Principato, A., Giardina, A., Tripodo, C., Porcasi, R., Peralta, S., Franco, V., Giardina, E., Craxi, A., Pitzalis, C. and Triolo, G. (2009), Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis. Arthritis & Rheumatism, 60: 955–965. doi: 10.1002/art.24389
- Issue published online: 30 MAR 2009
- Article first published online: 30 MAR 2009
- Manuscript Accepted: 17 DEC 2008
- Manuscript Received: 11 MAR 2008
- Ministero della Università e della Ricerca Scientifica of Italy
- Clinician Scientist Fellowship from the Arthritis Research Campaign
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).
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.
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-1β. Finally, while the Th1-related cytokines interferon-γ, 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.
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.