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程序性细胞死亡蛋白1及其配体调节变应性鼻炎中的免疫平衡

[Programmed cell death protein 1 and its ligands regulate immune balance in allergic rhinitis].

作者信息

Wen S L, Li F, Zhao F, Zuo J J, Deng Y Q, Zhang W, Tao Z Z

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Otorhinolaryngology Head and Neck Surgery Institute, Renmin Hospital of Wuhan University, Wuhan 430060, China.

出版信息

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Apr 7;55(4):384-390. doi: 10.3760/cma.j.cn115330-20190618-00392.

Abstract

To explore the expression and significance in regulating immune balance of programmed cell death protein 1 (PD-1) and its ligands PD-L1, PD-L2 in allergic rhinitis (AR). Eighty-two patients who received outpatient treatment due to high nasal reaction symptoms or were hospitalized due to nasal septum deviation and underwent nasal septum correction surgery in Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from May 2018 to May 2019 were enrolled, including 42 males and 40 females, with the age ranging from 14 to 38 years old. Blood, inferior turbinate nasal mucosal tissue and relevant clinical data were collected. Patients were divided into AR group and control group due to clinical manifestation, skin prick test and detection of specific IgE (sIgE) in serum. Immunohistochemistry was used to detect the expression of PD-1 and its ligands in nasal mucosa of the two groups. Flow cytometry was used to detect the proportions of PD-1(+)CD4(+)T cells, PD-L1(+) myeloid dendritic cells (mDCs), PD-L2(+)mDCs and Th2 cells in peripheral blood of the two groups. The expression levels of total IgE, sPD-1, sPD-L1 and sPD-L2 in serum of the two groups were detected by ELISA. The measurement data of normal distribution or normal distribution after the logarithm conversion to Ln were compared by test. correlation or correlation was used to analyze the correlation among the indicators. 0.05 was considered statistically significant. The expression of PD-1 and its ligands on the surface of immune cells in the nasal mucosa of the AR group was significantly higher than that of the control group. The ratio of PD-1(+)CD4(+)T cells, PD-L1(+)mDCs and Th2 cells in peripheral blood of AR group was significantly higher than that of the control group ((15.24±6.45)% (8.71±5.33)%, (8.79±2.01)% (5.74±2.90)%, (7.89±1.95)% (2.52±1.34)%, all 0.05). There was no significant difference in the ratio of PD-L2(+)mDCs between the two groups. Correlation analysis found that the proportion of PD-1(+)CD4(+) T cells was positively correlated with the Visual Analogue Scale (VAS) score of AR, total IgE concentration and the serum sIgE concentration ( value was 0.501, 0.541, 0.608, respectively, all 0.05). The proportion of PD-L1(+)mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration ( value was 0.604, 0.563, respectively, all 0.05). The proportion of Th2 cells in peripheral blood was positively correlated with the proportion of PD-L1(+)mDCs and PD-1(+)CD4(+)T cells ( value was 0.538, 0.623, respectively, all 0.05). Serum total IgE, sPD-1 and sPD-L1 in the AR group were significantly higher than those in the control group ((6.34±1.38) ng/ml (4.89±1.10) ng/ml, (4.40±1.01) pg/ml (3.79±1.21) pg/ml, (3.88±0.25) pg/ml (3.57±0.23) pg/ml, all 0.05), and there was no significant difference in sPD-L2 levels between the two groups. Correlation analysis showed that sPD-L1 was positively correlated with total IgE and sIgE concentration ( values was 0.32, 0.45, respectively, all 0.05). PD-1 and PD-L1 are highly expressed on the surface of immune cells in peripheral blood and nasal mucosa of AR patients, and sPD-1 and sPD-L1 expression levels in peripheral blood of AR patients are increased. The PD-1/PD-L1 signaling pathway promote AR inflammatory response by inducing Th2 type immune response.

摘要

探讨程序性细胞死亡蛋白1(PD-1)及其配体PD-L1、PD-L2在变应性鼻炎(AR)中调节免疫平衡的表达及意义。选取2018年5月至2019年5月在武汉大学人民医院耳鼻咽喉头颈外科因鼻高反应症状接受门诊治疗或因鼻中隔偏曲住院并行鼻中隔矫正手术的82例患者,其中男42例,女40例,年龄14~38岁。收集血液、下鼻甲鼻黏膜组织及相关临床资料。根据临床表现、皮肤点刺试验及血清特异性IgE(sIgE)检测将患者分为AR组和对照组。采用免疫组织化学法检测两组鼻黏膜中PD-1及其配体的表达。采用流式细胞术检测两组外周血中PD-1(+)CD4(+)T细胞、PD-L1(+)髓样树突状细胞(mDCs)、PD-L2(+)mDCs及Th2细胞的比例。采用酶联免疫吸附测定(ELISA)法检测两组血清中总IgE、可溶性PD-1(sPD-1)、可溶性PD-L1(sPD-L1)及可溶性PD-L2(sPD-L2)的表达水平。对正态分布或经对数转换为Ln后呈正态分布的计量资料采用t检验进行比较。采用Pearson相关或Spearman相关分析指标间的相关性。以P<0.05为差异有统计学意义。AR组鼻黏膜免疫细胞表面PD-1及其配体的表达明显高于对照组。AR组外周血中PD-1(+)CD4(+)T细胞、PD-L1(+)mDCs及Th2细胞的比例明显高于对照组(分别为(15.24±6.45)%比(8.71±5.33)%、(8.79±2.01)%比(5.74±2.90)%、(7.89±1.95)%比(2.52±1.34)%,均P<0.05)。两组间PD-L2(+)mDCs的比例差异无统计学意义。相关性分析发现,PD-1(+)CD4(+)T细胞的比例与AR的视觉模拟评分(VAS)、总IgE浓度及血清sIgE浓度呈正相关(r值分别为0.501、0.541、0.608,均P<0.05)。PD-L1(+)mDCs的比例与AR的VAS评分及血清sIgE浓度呈正相关(r值分别为0.604、0.563,均P<0.05)。外周血中Th2细胞的比例与PD-L1(+)mDCs及PD-1(+)CD4(+)T细胞的比例呈正相关(r值分别为0.538、0.623,均P<0.05)。AR组血清总IgE、sPD-1及sPD-L1明显高于对照组(分别为(6.34±1.38)ng/ml比(4.89±1.10)ng/ml、(4.40±1.01)pg/ml比(3.79±1.21)pg/ml、(3.88±0.25)pg/ml比(3.57±0.23)pg/ml,均P<0.05),两组间sPD-L2水平差异无统计学意义。相关性分析显示,sPD-L1与总IgE及sIgE浓度呈正相关(r值分别为0.32、0.45,均P<0.05)。AR患者外周血及鼻黏膜免疫细胞表面PD-1和PD-L1高表达,且AR患者外周血中sPD-1和sPD-L1表达水平升高。PD-1/PD-L1信号通路通过诱导Th2型免疫反应促进AR炎症反应。

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