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2型固有淋巴细胞在嗜酸粒细胞增多型鼻息肉发病机制中的作用

The role of type 2 innate lymphoid cells in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps

摘要目的 研究2型固有淋巴细胞(type 2 innate lymphoid cells,ILC2s)在不同分型鼻息肉中的分布特点,探讨ILC2s在嗜酸粒细胞增多型鼻息肉(eosinophilic chronic rhinosinusitis with nasal polyps,ECRSwNP)发病机制中的作用.方法 流式细胞分析健康下鼻甲黏膜组织(n=6)和鼻息肉组织(n=19)单细胞悬液中ILC2s、Th2细胞占CD45+细胞的比例.HE染色鼻息肉组织,按照嗜酸粒细胞计数不同分为ECRSwNP和非嗜酸粒细胞增多型鼻息肉(non-eosinophilic chronic rhinosinusitis with nasal polyps,non-ECRSwNP).采用Mann-WhitneyU检验ECRSwNP组(n=9)、non-ECRSwNP组(n=10)和对照组(n=6)中ILC2s、Th2细胞比例差异;采用Pearson相关系数分析ILC2s、Th2细胞比例与组织中嗜酸粒细胞计数的相关性;对比变应原阳性及阴性患者ILC2s比例差异.结果 与对照组和non-ECRSwNP组相比,ECRSwNP组的ILC2s比例升高,差异有统计学意义[(0.051 ±0.025)比(0.004±0.004),(0.051 ±0.025)比(0.011 ±0.017),Z值分别为-3.185、-3.186,P值均<0.05];对照组和non-ECRSwNP组间ILC2s比例的差异无统计学意义[(0.004±0.004)比(0.011 ±0.017),Z=-0.712,P=0.492].ECRSwNP组和non-ECRSwNP组的Th2细胞比例均较对照组显著升高,差异有统计学意义[(0.500 ±0.437)比(0.106 ±0.102),(0.275 ±0.170)比(0.106 ±0.102),Z值分别为-2.946、-2.278,P值均<0.05];但non-ECRSwNP组和ECRSwNP组间Th2细胞比例的差异无统计学意义[(0.275 ±0.170)比(0.500±0.437),Z=-1.306,P=0.211].ILC2s比例与Th2细胞比例成正相关(r =0.571,P=0.011);ILC2s比例与组织嗜酸粒细胞计数成正相关(r=0.579,P=0.009);Th2细胞比例与组织嗜酸粒细胞计数成正相关(r=0.844,P=0.001).变应原阳性患者的ILC2s比例高于变应原阴性患者,但差异没有统计学意义[(0.032 ±0.290)比(0.028 ±0.300),Z=-0.286,P =0.725].结论 ILC2s细胞比例在ECRSwNP中升高,并与Th2细胞、组织中嗜酸粒细胞计数成正相关,但在变应原阳性和阴性患者间无显著差异,提示这种固有免疫细胞在非变态反应诱发的ECRSwNP发病机制中具有意义.

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abstractsObjective To investigate the type 2 innate lymphoid cells (ILC2s) in eosinophilic nasal polyps,non-eosinophilic nasal polyps and controls,and to compare the characteristics of ILC2s indifferent types of nasal polyp.Methods Flow cytometric analysis was used to quantify the ILC2s and Th2 cells in tissues from 19 patients with chronic rhinosinusitis with nasal polyp (CRSwNP) and 6 controls.The patients were classified into two groups as eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) based on eosinophil counts under hematoxylin-eosin staining.ILC2 and Th2 cell frenquencies,measured as a percentage of CD45 + cells,were compared among ECRSwNP group (n =9),non-ECRSwNP group (n =10) and control group (n =6) using Mann-Whitney U test.The correlation between ILC2,Th2 cell frequencies and eosinophil count in tissues was analyzed using Pearson correlation coefficient.Results ILC2 frequencies in ECRSwNP group were significantly higher than non-ECRSwNP group and controls ((0.051 ± 0.025) vs (0.011 ±0.017),(0.051 ± 0.025) vs (0.004 ± 0.004),Z value was-3.185,-3.186,respectively,both P <0.05).There was no significant difference between ILC2 frequencies in non-ECRSwNP and controls ((0.011-0.017) vs (0.004 ±0.004),Z =-0.712,P =0.492).Th2 cell frequencies in ECRSwNP and non-ECRSwNP group were significantly higher than controls ((0.500 ± 0.437) vs (0.106 ± 0.102),(0.275 ± 0.170) vs (0.106 ± 0.102),Z value was-2.946,-2.278,respectively,both P < 0.05).There was no significant difference between Th2 frequencies in non-ECRSwNP group and ECRSwNP group ((0.275 ± 0.170) vs (0.500 ± 0.437),Z =-1.306,P =0.211).ILC2 frequencies significantly correlated with Th2 cell frequencies (r =0.571,P =0.011) and tissue eosinophilia (r =0.579,P =0.009).Th2 cell frequencies significantly correlated with tissue eosinophilia (r =0.844,P =0.001).There was no significant association between ILC2 and allergic status.Conclusion ILC2s are elevated in ECRSwNP,and not influenced by allergic status,suggesting that ILC2s play an important role in ECRSwNP without allergic diseases.

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