EGR2调控慢性鼻窦炎伴鼻息肉患者Th17/Treg失衡的分子机制  

Regulatory effect of EGR2 on Treg/Th17 immune imbalance in patients with chronic sinusitis

作　　者：冯桦 简恒恒 李雪 马祖霞 Feng Hua;Jian Hengheng;Li Xue;Ma Zuxia(Department of Otolaryngology,the Third Affiliated Hospital of Zunyi Medical University,the First People’s Hospital of Zunyi,Zunyi Guizhou 563000,China)

机构地区：[1]遵义医科大学第三附属医院,遵义市第一人民医院耳鼻咽喉科,贵州遵义563000

出　　处：《遵义医科大学学报》2023年第5期475-483,共9页Journal of Zunyi Medical University

基　　金：遵义市汇川区科技局项目(NO:遵汇科合201719);贵州省科学技术基金资助项目[NO:黔科合基础(2018)1182];遵义市科技局项目[NO:遵市科合社字(2017)49]。

摘　　要：目的探究EGR2介导慢性鼻窦炎伴鼻息肉患者Th17/Treg细胞失衡的分子机制。方法选取2021年7月—2022年9月就诊于我院的CRSwNP患者50例,根据SPT检测结果分为Non-atopic CRSwNP组(n=23)和Atopic CRSwNP组(n=27),同期因鼻中隔偏曲、单纯上颌窦囊肿接受手术的患者作为Control组(n=25)。分别取患者鼻息肉及鼻腔、鼻窦粘膜,采用WB法测鼻组织EGR2、IL-17A、FOXP3、STAT3和p-STAT3的表达,Elisa法测外周血中EGR2、IL-17A、TGF-β1的表达;分选培养CD4+T细胞,SiRNA敲低CD4+T细胞中EGR2表达,WB法检测EGR2、IL-17A、FOXP3、STAT3和p-STAT3的表达。结果3组患者鼻组织中EGR2和FOXP3表达比较,Atopic CRSwNP组<Non-atopic CRSwNP组<Control组(P<0.05);IL-17A和p-STAT3表达比较,Atopic CRSwNP组>Non-atopic CRSwNP组>Control组(P<0.05)。3组患者外周血中EGR2和TGF-β1含量比较,Atopic CRSwNP组<Non-atopic CRSwNP组<Control组(P<0.05);IL-17A含量比较,Atopic CRSwNP组>Non-atopic CRSwNP组>Control组(P<0.05)。3组患者外周血中EGR2含量与TGF-β1含量呈正相关(r=0.616,P<0.05),与IL-17A含量呈负相关(r=-0.587,P<0.05)。较于Negative Control组,SiRNA组的STAT3表达无差异(P>0.05),p-STAT3和IL-17A表达增加(P<0.05),EGR2和FOXP3表达降低(P<0.05)。结论Atopic CRSwNP组和Non-atopic CRSwNP组患者息肉组织和外周血中均存在Th17/Treg细胞失衡,且Atopic CRSwNP患者更严重;EGR2低表达可能是CRSwNP患者Th17/Treg细胞失衡的重要因素,低表达的EGR2增加STAT3磷酸化,从而导致CD4+T细胞过度分化为Th17细胞,同时抑制Treg细胞产生。Objective To investigate the molecular mechanism of EGR2-mediated Th17/Treg cell imbalance in patients with chronic rhinosinusitis with nasal polyps.Methods Fifty patients with CRSwNP who visited our hospital from July 2021 to September 2022 were selected and divided into non-atopic CRSwNP group(23 patients)and atopic CRSwNP group(27 patients)according to SPT test results,and patients who underwent surgery for nasal septal deviation and simple maxillary sinus cyst during the same period served as the control group(25 patients).Nasal polyps and nasal and sinus mucosa were taken from the patients respectively,and the expression of EGR2,IL-17A,FOXP3,STAT3 and p-STAT3 in nasal tissue was measured by WB method,and the expression of EGR2,IL-17A and TGF-β1 in peripheral blood was measured by Elisa method.CD4+T cells were sorted and cultured,SiRNA knocked down EGR2 expression in CD4+T cells,and then the expression of EGR2,IL-17A,FOXP3,STAT3 and p-STAT3 was measured by WB method.Results When comparing the expression of EGR2 and FOXP3 in the nasal tissues of the three groups of patients,Atopic CRSwNP group<Non-atopic CRSwNP group<control group(P<0.05);when comparing the expression control group(P<0.05);when comparing the expression of IL-17A and p-STAT3 in the nasal tissues of the three groups of patients,Atopic CRSwNP group>Non-atopic CRSwNP group>control group(P<0.05).When comparing the levels of EGR2 and TGF-β1 in the peripheral blood of the 3 groups,Atopic CRSwNP group>Non-atopic CRSwNP group>control group(P<0.05);when comparing the levels of IL-17A in the peripheral blood of the 3 groups,Atopic CRSwNP group>Non-atopic CRSwNP group>control group(P<0.05).There was a positive correlation between EGR2 and TGF-β1 levels in peripheral blood(r=0.616,P<0.05)and a negative correlation between EGR2 and IL-17A levels(r=-0.587,P<0.05)in the three groups.Compared to the Negative Control group,there was no difference in STAT3 expression in the SiRNA group(P>0.05),and p-STAT3 and IL-17A expression was increased(P<0.05),and EGR2 a

关 键 词：EGR2 慢性鼻窦炎 鼻息肉 Th17/Treg细胞失衡 

分 类 号：R765.4[医药卫生—耳鼻咽喉科]