目的 分析过敏性鼻炎(allergic rhinitis，AR)患者外周血CD4＋Th17细胞中IL-18、IL-18结合蛋白a(IL-18-binding protein a, IL-18BPa)和IL-18受体α(IL-18 receptor α，IL-18Rα)的表达水平及过敏原对其表达的影响。 方法 选择2019年10月—2020年9月锦州医科大学附属第一医院过敏反应科门诊AR患者45例和该医院体检中心体检者23例(健康对照组)为研究对象。根据皮肤点刺试验结果，将患者分为阳性组(AR组，24例)和阴性组(nAR组，21例)。收集受试者血液样本，流式细胞术检测过敏原对CD4＋Th17细胞中IL-18、IL-18BPa和IL-18Rα蛋白质表达水平的影响。Bioplex检测血浆中IL-17A水平，并分析其与IL-18＋Th17细胞比例的相关性。 结果 与健康对照组比较，AR组患者CD4＋Th17细胞和IL-18＋Th17细胞比例均增加(P<0.01)，IL-18BPa＋Th17细胞比例降低(P<0.01)，IL-18BPa的平均荧光强度(mean fluorescence intensity，MFI)增加(P<0.01)，IL-18Rα的MFI降低(P<0.01)；nAR组患者CD4＋Th17细胞IL-18BPa的MFI增加(P<0.000 1)，IL-18Rα的MFI降低(P<0.000 1)。与nAR组患者比较，AR组患者IL-18＋Th17细胞比例(P<0.05)和IL-18Rα的MFI均增加(P<0.01)。户尘螨和梧桐花粉过敏原粗提液能分别诱导AR组患者IL-18＋Th17和IL-18BPa＋Th17细胞比例增加(P<0.05)。户尘螨过敏原粗提液可直接诱导分选后的健康对照者CD4＋Th17细胞表达IL-18和IL-18Rα(P<0.05)。AR组患者血浆IL－17A水平升高(P<0.001)，并与IL-18＋Th17细胞比例中度相关(P<0.05)。 结论 过敏原可能通过诱导外周血CD4＋Th17细胞表达IL-18和IL-18Rα参与AR发病。 Objective To investigate the expression of IL-18, IL-18-binding protein a(IL-18BPa) and IL-18 receptor α(IL-18Rα) by peripheral blood CD4 + Th17 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods This study enrolled 45 outpatients with AR and 23 healthy control subjects receiving physical examination in the First Affiliated Hospital of Jinzhou Medical University from October 2019 to September 2020. According to the results of skin prick test, the 45 patients were divided into two groups: AR group with positive results (24 cases) and nAR group with negative results (21 cases). Blood samples of them were collected. Flow cytometry was used to analyze the effects of allergens on the expression of IL-18, IL-18BPa and IL-18Rα at protein level by peripheral blood CD4+ Th17 cells. The level of IL-17A in plasma was measured by Bioplex system, and its correlation with the percentage of IL-18+ Th17 cells was analyzed. Results Compared with the healthy control group, the AR group showed increased ratios of CD4+ Th17 and IL-18+ Th17 cells (P<0.01), decreased ratio of IL-18BPa+ Th17 cells (P<0.01), enhanced mean fluorescence intensity (MFI) of IL-18BPa (P<0.01) and reduced MFI of IL-18Rα (P<0.01) the nAR group showed enhanced MFI of IL-18BPa (P<0.000 1) and reduced MFI of IL-18Rα (P<0.000 1). The ratio of IL-18+ Th17 cells and the MFI of IL-18Rα in the AR group were higher than those in the nAR group (P<0.05,P<0.01). House dust mite extract andPlatanus pollen extract induced the expression of IL-18 and IL-18BPa by CD4+ Th17 cells of AR patients (P<0.05). Moreover, house dust mite extract directly induced the CD4+ Th17 cells isolated from the healthy control subjects to express IL-18 and IL-18R (P<0.05). Compared with healthy control subjects, AR patients had higher level of IL-17A in plasma and it was moderately correlated with the ratio of IL-18+ Th17 cells (P<0.05). Conclusions Allergens may be involved in the pathogenesis of AR by inducing blood CD4+ Th17 cells to express IL-18 and IL-18Rα.
Effects of allergens on the expression of IL-18, IL-18-binding protein a and IL-18 receptor α by peripheral blood CD4+ Th17 cells of patients with allergic rhinitis
Objective To investigate the expression of IL-18, IL-18-binding protein a(IL-18BPa) and IL-18 receptor α(IL-18Rα) by peripheral blood CD4 + Th17 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expression. Methods This study enrolled 45 outpatients with AR and 23 healthy control subjects receiving physical examination in the First Affiliated Hospital of Jinzhou Medical University from October 2019 to September 2020. According to the results of skin prick test, the 45 patients were divided into two groups: AR group with positive results (24 cases) and nAR group with negative results (21 cases). Blood samples of them were collected. Flow cytometry was used to analyze the effects of allergens on the expression of IL-18, IL-18BPa and IL-18Rα at protein level by peripheral blood CD4+ Th17 cells. The level of IL-17A in plasma was measured by Bioplex system, and its correlation with the percentage of IL-18+ Th17 cells was analyzed. Results Compared with the healthy control group, the AR group showed increased ratios of CD4+ Th17 and IL-18+ Th17 cells (P<0.01), decreased ratio of IL-18BPa+ Th17 cells (P<0.01), enhanced mean fluorescence intensity (MFI) of IL-18BPa (P<0.01) and reduced MFI of IL-18Rα (P<0.01) the nAR group showed enhanced MFI of IL-18BPa (P<0.000 1) and reduced MFI of IL-18Rα (P<0.000 1). The ratio of IL-18+ Th17 cells and the MFI of IL-18Rα in the AR group were higher than those in the nAR group (P<0.05,P<0.01). House dust mite extract andPlatanus pollen extract induced the expression of IL-18 and IL-18BPa by CD4+ Th17 cells of AR patients (P<0.05). Moreover, house dust mite extract directly induced the CD4+ Th17 cells isolated from the healthy control subjects to express IL-18 and IL-18R (P<0.05). Compared with healthy control subjects, AR patients had higher level of IL-17A in plasma and it was moderately correlated with the ratio of IL-18+ Th17 cells (P<0.05). Conclusions Allergens may be involved in the pathogenesis of AR by inducing blood CD4+ Th17 cells to express IL-18 and IL-18Rα.
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