白细胞介素-23在炎症性肠病的表达升高并诱导促炎细胞因子分泌

Increased expression of interleukin-23 induces proinflammatory cytokine secretion in inflammatory bowel disease

目的通过分析白细胞介素（IL）-23p19及其受体（IL-23R）在炎症性肠病（IBD）患者中的表达，研究IL-23对IBD患者外周血T细胞激活和效应应答的影响，探讨其在疾病发生过程中的免疫病理作用。方法收集12例克罗恩病（CD）患者、25例溃疡性结肠炎（UC）患者和20名继康者外周血和肠黏膜组织活俭标本，使用免疫组化染色和逆转录（RT）-PCR分析IL-23p19表达，分离外周血单个核细胞（PBMC）和肠黏膜固有层内单个核细胞（LPMC），利用流式细胞仪检测IL-23R在CD4^＋、CD8^＋T细胞和自然杀伤（NK）细胞表面表达。体外培养PBMC．使用IL-23和抗CD3单抗体外刺激，使用酶联免疫吸附试验愉测肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和白细胞介素（IL）-2分泌。结果IBD患者炎症肠黏膜组织内IL-23p19蛋白和mRNA表达水平比健康对照者显著升高（P〈0．05）。IL-23R在IBD患者外周血和肠黏膜固有层组织内CD4^＋、CD8^＋T细胞和NK细胞表达水平也比健康者显著升高（P〈0．05）。体外培养PBMC，使用IL-23刺激，发现IL-23可显著诱导IBD患者，尤其是CD患者PBMC激活，分泌高水平TNF-α、IFN-γ和IL-2（P〈0．05）。结论IL-23及其受体在IBD患者炎症肠黏膜组织中表达升高．IL-23可诱导IBD患者淋巴细胞分泌高水平的炎性介质，提示IL-23参与了肠黏膜炎症损伤，阻断IL-23生物学效应可能治疗IBD。

Objective To analyze expression of interleukin （IL）-23p19 and IL-23 receptor （IL- 23R） in inflammatory bowel disease （IP, D）, and the role in the induction of peripheral blood T cell activation and proinflammatory eytokine secretion. Methods Peripheral blood （PB） and intestinal mucosal biopsies were collected from 12 patients with Crohn＇s disease （CD）, 25 patients with ulcerative colitis （UC） and 20 heahhy controls. Expression of IL-23p19 was determined by immunohistochemistry and RT-PCR. IL-23R expression in CD4^＋ , CD8^＋ T and NK cells from peripheral blood and lamina propria was analyzed by flow cytometry, Peripheral blood mononuclear cells （PBMC） were isolated and cuhured under stimulation with IL-23 and anti-CD3, and the levels of tumor necrosis factor α （TNFα） interferon （IFN）γ and IL-2 were determined by enzyme-linked immunosorbent assay （ELISA）. Results The expression of IL-23p19 was significantly increased in inflamed rnucosa of CD at both the transcriptional and translational levels compared with that in UC and healthy controls. IL-23R was mainly expressed in PB- and lamina propria-CD4^＋ , CD8^＋ T cells and NK cells from IBD patients, and markedly increased compared with controls （P〈0.05）. IL- 23 strongly triggered PBMC from IBD patients to produce significantly higher levels of IFN-γ, TNF-α and IL-2 （P〈0.05）. Conclusions IL-23p19 and IL-23R are highly expressed in IBD, particularly in CD, and may play an important role in the induction of T cell activation and proinflammatory cytokine secretion, suggesting that targeted therapy directed against IL-23 may have a therapeutic role in IBD.