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Title: [Programmed cell death protein 1 and its ligands regulate immune balance in allergic rhinitis].
Author: Wen SL, Li F, Zhao F, Zuo JJ, Deng YQ, Zhang W, Tao ZZ.
Journal: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi; 2020 Apr 07; 55(4):384-390. PubMed ID: 32306637.
Abstract:
Objective: 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). Methods: 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 t test. Pearson correlation or Spearman correlation was used to analyze the correlation among the indicators. P<0.05 was considered statistically significant. Results: 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)% vs (8.71±5.33)%, (8.79±2.01)% vs (5.74±2.90)%, (7.89±1.95)% vs (2.52±1.34)%, all P<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 (r value was 0.501, 0.541, 0.608, respectively, all P<0.05). The proportion of PD-L1(+)mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration (r value was 0.604, 0.563, respectively, all P<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 (r value was 0.538, 0.623, respectively, all P<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 vs (4.89±1.10) ng/ml, (4.40±1.01) pg/ml vs (3.79±1.21) pg/ml, (3.88±0.25) pg/ml vs (3.57±0.23) pg/ml, all P<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 (r values was 0.32, 0.45, respectively, all P<0.05). Conclusions: 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. 目的： 探讨程序性死亡受体1（PD-1）及其配体PD-L1、PD-L2在变应性鼻炎（AR）中的表达及其对AR免疫偏移的调控作用。 方法： 收取2018年5月至2019年5月，因鼻腔高反应症状于武汉大学人民医院耳鼻咽喉头颈外科门诊就诊，或因鼻中隔偏曲住院行鼻中隔矫正手术的82例患者，男42例，女40例，年龄14~38岁。收集相应患者的临床资料、血液、下鼻甲黏膜标本。根据临床表现、皮肤点刺试验和血清特异性变应原筛查特异性IgE（sIgE）检测结果，将患者分为AR组和对照组。免疫组织化学法检测鼻黏膜中PD-1及配体的表达情况。流式细胞术检测外周血PD-1(+)CD4(+)T细胞、PD-L1(+)髓样树突状细胞（mDCs）、PD-L2(+)mDCs及Th2细胞比例。酶联免疫吸附（ELISA）法检测血清中总IgE、PD-1及配体分泌型（sPD-1、sPD-L1、sPD-L2）的表达水平。正态分布或经Ln转换后呈正态分布的计量资料组间比较采用t检验，相关性分析采用Spearman或Pearson相关，设P<0.05为差异有统计学意义。 结果： AR组鼻黏膜中免疫细胞表面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、Th2细胞比例明显高于对照组[（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）%，P值均<0.05]，两组PD-L2(+)mDCs比例无明显差异。PD-1(+)CD4(+)T细胞比例与AR病情总体视觉模拟量表（VAS）评分、血清总IgE、sIgE浓度呈正相关（r值分别为0.501、0.541、0.608，P值均<0.05），PD-L1(+)mDCs比例与AR病情总体VAS评分、sIgE浓度呈正相关（r值分别为0.604、0.563，P值均<0.05），Th2细胞比例与PD-L1(+)mDCs、PD-1(+)CD4(+)T细胞比例呈正相关（r值分别为0.538、0.623，P值均<0.05）。AR组sPD-1、sPD-L1及总IgE表达水平较对照组明显升高[（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、（6.34±1.38） ng/ml比（4.89±1.10） ng/ml，P值均<0.05]，sPD-L2表达水平无明显差异。相关性分析发现sPD-L1与总IgE、sIgE浓度呈正相关（r值分别为0.32、0.45，P值均<0.05）。 结论： AR患者外周血及鼻黏膜组织中免疫细胞表面均高表达PD-1及PD-L1，AR患者外周血中sPD-1及sPD-L1表达水平升高，PD-1/PD-L1信号通路可通过诱导Th2型免疫反应促进AR炎性反应。.

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