Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis
Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis
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DOI：
10.1002/art.34355
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发表时间：
2012-06-01
影响因子：
--
通讯作者：
Triolo, Giovanni
中科院分区：
文献类型：
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作者：
Ciccia, Francesco;Accardo-Palumbo, Antonina;Triolo, Giovanni
目的强直性脊柱炎（AS）患者肠道炎症反应以白细胞介素-23（IL-23）过度表达为特征。已知IL-23通过固有层NKp 44+自然杀伤（NK）细胞调节IL-22产生，所述NK细胞被认为参与保护性粘膜机制。本研究旨在评估AS患者回肠中NKp 44 + NK细胞的频率和IL-22的表达。方法采用流式细胞仪检测组织中NKp 44 + NK细胞、NKp 46 + NK细胞和IL-22产生细胞。采用逆转录聚合酶链反应对15例AS患者、15例克罗恩病（CD）患者和15例健康对照者的回肠标本进行IL-22、IL-23、IL-17、STAT-3和粘蛋白1（MUC-1）的定量基因表达分析。通过免疫组织化学分析NKp 44、pSTAT-3和IL-22表达。结果与CD患者和对照组相比，AS患者炎症回肠中NKp 44 + NK细胞的频率增加，而NKp 46 + NK细胞的频率没有增加。NKp 46 + NK细胞的频率仅在CD患者中显著增加。在CD 4+淋巴细胞和NKp 44 + NK细胞亚群中，后者是AS患者固有层单核细胞上IL-22的主要来源。AS患者回肠末端IL-22、IL-23 p19、MUC-1和STAT-3转录物显著上调。免疫组化分析证实AS和CD患者炎症粘膜中IL-22和pSTAT-3表达增加。结论AS患者肠道组织中IL-22表达增加，产生IL-22的NKp 44 + NK细胞数量增加，可能具有组织保护作用。
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.