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[白细胞介素17A在非嗜酸性粒细胞性鼻息肉慢性鼻窦炎中的表达及细胞来源]

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

作者信息

Chen X H, Chang L H, Huang J C, Li X, Lai X P, Wu X F, Huang Z Z, Wang Z Y, Bao H W, Zhang G H

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

出版信息

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Jun 7;55(6):604-610. doi: 10.3760/cma.j.cn115330-20190702-00419.

DOI:10.3760/cma.j.cn115330-20190702-00419
PMID:32610404
Abstract

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. 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. 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 (()) 9.42 (11.33) pg/ml, 10.21%±1.54% (±) 3.93%±0.80%, =2.95, =3.62, all <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 8.27 (12.51) pg/ml, (5.44±0.34) pg/ml (4.17±0.22) pg/ml, =2.426, =2.29, all <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 (=0.615, =0.009). No positive correlation between IL-17A and TGF-β or IL-23 was observed. 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.

摘要

探讨白细胞介素17A(IL-17A)在非嗜酸性粒细胞性慢性鼻-鼻窦炎伴鼻息肉(nECRSwNP)中的表达及细胞来源,并分析其表达差异的可能原因。收集2017年1月至2018年5月在中山大学附属第三医院接受功能性鼻内镜鼻窦手术的14例嗜酸性粒细胞性慢性鼻-鼻窦炎伴鼻息肉(ECRSwNP)患者和28例nECRSwNP患者的样本,其中男性33例,女性9例,年龄18至65岁。采用酶联免疫吸附测定(ELISA)和流式细胞术研究ECRSwNP组和nECRSwNP组鼻组织中IL-17A的表达及细胞来源。然后通过流式细胞术分析ECRSwNP组和nECRSwNP组中产生IL-17A的主要细胞数量和分化能力的差异。最后,通过ELISA分析IL-6、转化生长因子-β(TGF-β)和IL-23的表达,它们被认为是促进CRSwNP中Th17/Tc17分化的重要因素及其与IL-17A的相关性。使用IBM SPSS 20进行统计分析。nECRSwNP组的IL-17A蛋白水平和IL-17A(+)淋巴细胞百分比高于ECRSwNP组(158.56(167.76)pg/ml(())9.42(11.33)pg/ml,10.21%±1.54%(±)3.93%±0.80%,=2.95,=3.62,均<0.01)。Tc17细胞(产生IL-17A的CD8(+)T细胞)和Th17细胞(产生IL-17A的CD4(+)T细胞)是ECRSwNP组和nECRSwNP组中IL-17A的主要产生细胞。进一步分析显示,ECRSwNP组和nECRSwNP组之间CD8(+)和CD4(+)T细胞数量无显著差异,但nECRSwNP组中CD8(+)和CD4(+)T细胞分化为Tc17和Th17的能力强于ECRSwNP组。与ECRSwNP组相比,nECRSwNP组中也发现了被认为是促进Th17/Tc17分化的重要因素IL-6和TGF-β的高表达(56.07(234.25)pg/ml 8.27(12.51)pg/ml,(5.44±0.34)pg/ml(4.17±0.22)pg/ml,=2.426,=2.29,均<0.05)。但两组间IL-23表达差异无统计学意义。此外,IL-17A的表达与IL-6呈显著正相关(=0.615,=0.009)。未观察到IL-17A与TGF-β或IL-23之间的正相关。nECRSwNP患者鼻黏膜中IL-17A的表达明显高于ECRSwNP患者,这是由于Tc17/Th17细胞表达和分化增加所致。在CRSwNP中,IL-17A与IL-6呈正相关,IL-6是促进Th17/Tc17分化的重要因素。

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