Drs. Ciccia and Accardo-Palumbo contributed equally to this work.
Interleukin-22 and interleukin-22–producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis
Version of Record online: 25 MAY 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 6, pages 1869–1878, June 2012
How to Cite
Ciccia, F., Accardo-Palumbo, A., Alessandro, R., Rizzo, A., Principe, S., Peralta, S., Raiata, F., Giardina, A., De Leo, G. and Triolo, G. (2012), Interleukin-22 and interleukin-22–producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis. Arthritis & Rheumatism, 64: 1869–1878. doi: 10.1002/art.34355
- Issue online: 25 MAY 2012
- Version of Record online: 25 MAY 2012
- Accepted manuscript online: 27 DEC 2011 02:57PM EST
- Manuscript Accepted: 20 DEC 2011
- Manuscript Received: 1 FEB 2011
- Ministero della Università e della Ricerca Scientifica of Italy
The intestinal inflammation observed in patients with ankylosing spondylitis (AS) is characterized by an overexpression of interleukin-23 (IL-23). IL-23 is known to regulate IL-22 production through lamina propria NKp44+ natural killer (NK) cells, which are thought to be involved in protective mucosal mechanisms. This study was undertaken to evaluate the frequency of NKp44+ NK cells and the expression of IL-22 in the ileum of AS patients.
Tissue NKp44+ NK cells, NKp46+ NK cells, and IL-22–producing cells were analyzed by flow cytometry. Quantitative gene expression analysis of IL-22, IL-23, IL-17, STAT-3, and mucin 1 (MUC-1) was performed by reverse transcriptase–polymerase chain reaction on ileal samples from 15 patients with AS, 15 patients with Crohn's disease (CD), and 15 healthy controls. NKp44, pSTAT-3, and IL-22 expression was analyzed by immunohistochemistry.
The frequency of NKp44+ but not NKp46+ NK cells was increased in the inflamed ileum of AS patients compared to CD patients and controls. The frequency of NKp46+ NK cells was significantly increased only in CD patients. Among CD4+ lymphocytes and NKp44+ NK cell subsets, the latter were the major source of IL-22 on lamina propria mononuclear cells from AS patients. Significant up-regulation of IL-22, IL-23p19, MUC-1, and STAT-3 transcripts in the terminal ileum of patients with AS was observed. Immunohistochemical analysis confirmed the increased IL-22 and pSTAT-3 expression in inflamed mucosa from AS and CD patients.
Our findings indicate that overexpression of IL-22, together with an increased number of IL-22–producing NKp44+ NK cells, occurs in the gut of AS patients, where it appears to play a tissue-protective role.