Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis

被引:105
作者
Ciccia, Francesco
Accardo-Palumbo, Antonina [2 ]
Alessandro, Riccardo
Rizzo, Aroldo [2 ]
Principe, Simona
Peralta, Sergio
Raiata, Francesca [2 ]
Giardina, AnnaRita
De Leo, Giacomo
Triolo, Giovanni [1 ]
机构
[1] Univ Palermo, Dept Internal Med, Div Rheumatol, I-90127 Palermo, Italy
[2] Azienda Osped Osped Riuniti Villa Sofia Cervello, Palermo, Italy
来源
ARTHRITIS AND RHEUMATISM | 2012年 / 64卷 / 06期
关键词
PROINFLAMMATORY GENE-EXPRESSION; ROR-GAMMA-T; CROHNS-DISEASE; INTESTINAL INFLAMMATION; NKP46(+) CELLS; MOUSE MODEL; IL-22; DIFFERENTIATION; MIGRATION; PATHOLOGY;
D O I
10.1002/art.34355
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective 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. Methods Tissue NKp44+ NK cells, NKp46+ NK cells, and IL-22producing 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 transcriptasepolymerase 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. Results 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. Conclusion Our findings indicate that overexpression of IL-22, together with an increased number of IL-22producing NKp44+ NK cells, occurs in the gut of AS patients, where it appears to play a tissue-protective role.
引用
收藏
页码:1869 / 1878
页数:10
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