title: Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ciccia
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
authors.forename: Alfonso
authors.initials: A
authors.lastname: Principato
authors.forename: Annarita
authors.initials: A
authors.lastname: Giardina
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Rossana
authors.initials: R
authors.lastname: Porcasi
authors.forename: Sergio
authors.initials: S
authors.lastname: Peralta
authors.forename: Vito
authors.initials: V
authors.lastname: Franco
authors.forename: Ennio
authors.initials: E
authors.lastname: Giardina
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxi
authors.forename: Costantino
authors.initials: C
authors.lastname: Pitzalis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Triolo