[Expression and cellular provenance of interleukin 17A in non-eosinophilic chronic rhinosinusitis with nasal polyps].

Objective: To investigate the expression and cellular provenance of interleukin 17A (IL-17A) in non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP), and to analyze the possible reasons for its different expression. Methods: Samples were collected from 14 patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and 28 patients with nECRSwNP, who underwent functional endoscopic sinus surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to May 2018, including 33 males and 9 females, with the age ranging from 18 to 65 years old. Enzyme linked immune sorbent assay (ELISA) and flow cytometry were used to investigate the expression and cellular origins of IL-17A in the nasal tissue of ECRSwNP and nECRSwNP groups. Then the difference of quantity and differentiation ability of the major cells producing IL-17A between ECRSwNP and nECRSwNP groups were analyzed by flow cytometry. Finally, the expressions of IL-6, transforming growth factor-β(TGF-β), and IL-23, which were considered as the important factors in promoting Th17/Tc17 differentiation in CRSwNP and their correlation with IL-17A, were analyzed by ELISA. Statistical analysis was performed using IBM SPSS 20. Results: The IL-17A protein levels and IL-17A(+)lymphocyte percentages were higher in nECRSwNP group compared with that of the ECRSwNP group (158.56 (167.76) pg/ml (M(QR)) vs. 9.42 (11.33) pg/ml, 10.21%±1.54% (x±s) vs. 3.93%±0.80%, Z=2.95, t=3.62, all P<0.01). Tc17 cells (CD8(+)T cells producing IL-17A) and Th17 cells (CD4(+)T cells producing IL-17A) were major IL-17A producers in both ECRSwNP and nECRSwNP group. Further analysis revealed that there was no significant difference in quantity of CD8(+)and CD4(+)T cells between ECRSwNP and nECRSwNP group, but the differentiation ability about CD8(+)and CD4(+)T cells differentiating into Tc17 and Th17 in nECRSwNP group was stronger than that in ECRSwNP. The high expressions of IL-6 and TGF-β, which were considered as the important factors in promoting Th17/Tc17 differentiation were also found in nECRSwNP group compared with ECRSwNP (56.07 (234.25) pg/ml vs. 8.27 (12.51) pg/ml, (5.44±0.34) pg/ml vs. (4.17±0.22) pg/ml, Z=2.426, t=2.29, all P<0.05). But the difference in expression of IL-23 was not significant difference between the two groups. Moreover, the expression of IL-17A showed significantly positive correlation with IL-6 (r=0.615, P=0.009). No positive correlation between IL-17A and TGF-β or IL-23 was observed. Conclusions: The expression of IL-17A in nasal mucosa of nECRSwNP patients is significantly higher than that of ECRSwNP, which is due to the increase of expression and differentiation of Tc17/Th17 cells. IL-17A shows positive correlation with IL-6 in CRSwNP, which is the important factor in promoting Th17/Tc17 differentiation.目的： 探讨非嗜酸粒细胞性慢性鼻窦炎伴鼻息肉（non-eosinophilic chronic rhinosinusitis with nasal polyps，nECRSwNP）中白细胞介素（interleukin，IL）17A的表达、细胞来源及表达差异的可能原因。 方法： 收集2017年1月至2018年5月在中山大学附属第三医院耳鼻咽喉头颈外科住院并行鼻内镜手术治疗的42例慢性鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps，CRSwNP）患者的组织标本，其中男33例，女9例，年龄18~65岁。嗜酸粒细胞性慢性鼻窦炎伴鼻息肉（eosinophilic chronic rhinosinusitis with nasal polyps，ECRSwNP）组14例，nECRSwNP组28例。酶联免疫吸附测定（ELISA）法检测IL-17A在2组鼻黏膜组织中的表达，流式细胞术检测IL-17A在2组中的表达及来源细胞；并探讨IL-17A主要来源细胞在2组中数量及分化能力的差异；通过ELISA分析促产IL-17A细胞分化的细胞因子在CRSwNP中的表达及与IL-17A的相关性。运用SPSS 20.0进行统计学分析。 结果： nECRSwNP组鼻黏膜组织中IL-17A的蛋白表达水平及产IL-17A的淋巴细胞比例均显著高于ECRSwNP组，差异均有统计学意义{158.56（167.76） pg/ml[M（QR），后同]比9.42（11.33） pg/ml，10.21%±1.54%（i±s，后同）比3.93%±0.80%，Z=2.95，t=3.62，P值均<0.01}。nECRSwNP组和ECRSwNP组中IL-17A均主要来源于Tc17细胞（产IL-17A的CD8(+)T细胞）和Th17细胞（产IL-17A的CD4(+)T细胞）。ECRSwNP组与nECRSwNP组中CD8(+)和CD4(+)T细胞比例无明显差异，但nECRSwNP组中CD8(+)和CD4(+)T细胞分化为Tc17和Th17细胞的能力强于ECRSwNP组。nECRSwNP组中促Tc17/Th17细胞分化的细胞因子IL-6和转化生长因子β（transforming growth factor -β，TGF-β）的表达均显著高于ECRSwNP组[56.07（234.25） pg/ml比8.27（12.51） pg/ml，（5.44±0.34） pg/ml比（4.17±0.22） pg/ml，Z=2.426，t=2.294，P值均<0.05]，但IL-23在2组间的差异无统计学意义。IL-17A与IL-6之间存在正相关关系（r=0.615，P=0.009），IL-17A与TGF-β之间、IL-17A与IL-23之间无相关性。 结论： nECRSwNP患者鼻黏膜中IL-17A的表达显著高于ECRSwNP，为Tc17/Th17细胞的表达及分化增加所致；IL-17A与促Tc17/Th17分化的细胞因子（IL-6）呈正相关关系。.