探讨CRTh2、CysLT1R及H1R在支气管哮喘患者外周血CD3+CD56+NKT细胞中的表达

The investigation on the expressions of CRTh2, CysLT1R and H1R in peripheral blood CD3+CD56+NKT cells of patients with bronchial asthma

摘要:

目的： 探讨Th2细胞趋化因子同源分子（chemoattractant receptor homologous molecule expressed on Th2 cells，CRTh2）、半胱氨酸白三烯受体1（cysteinyl leukotriene 1 receptor，CysLT1R）及组胺1型受体（histamine 1 receptor，H1R）在支气管哮喘（bronchial asthma，BA）患者外周血CD3⁺CD56⁺自然杀伤T细胞（natural killer T cells，NKT）中的表达情况及临床意义。方法： 收集2020年9月至2021年9月锦州医科大学附属医院BA患者（BA组，n=40）和健康对照组（healthy control，HC组，n=38）的外周血，流式细胞仪检测BA组和HC组外周血中CRTh2、CysLT1R及H1R在CD3⁺CD56⁺标记的NKT细胞上的表达，同时对其与血清总IgE（total immunoglobulin E，TIgE）、呼出气一氧化氮（fractional exhaled nitric oxide，FeNO）及肺功能第一秒用力呼气量/用力肺活量%（forced expiratory volume in the first second/forced vital capacity%，FEV1/FVC%）的相关性分析。结果： BA组[22.50（15.78，29.20）]外周血CD3⁺CD56⁺NKT细胞百分比较HC组[27.90（21.50，32.45）]降低（P=0.024）；进一步比较BA组[70.05（63.20，78.45）]CD3⁺淋巴细胞百分比低于HC组[73.70（69.88，79.38）]（P=0.035）。BA组[0.08（0.05，0.17）]CysLT1R百分比较HC组[0.16（0.10，0.34）]降低（P=0.004）；BA组CRTH2、H1R百分比[1.12（0.53，1.88）；5.21（1.41，10.10）]与HC组[1.17（0.60，4.25）；4.61（1.42，8.53）]比较，无统计学差异（P=0.234；P=0.697）。进一步对比CRTh2、H1R的平均荧光强度（mean fluorescence intensity，MFI），BA组[925.52（623.50，1 279.25）]CRTh2 MFI较HC组[1 345.50（891.00，1 977.75）]降低（P=0.002）；BA组[769（657.50，975.00）]H1R MFI与HC组[835.00（560.00，959.25）]无统计学差异（P=0.834）。CD3⁺CD56⁺NKT细胞与血清TIgE、FeNO无明显相关性（r=-0.052、r=0.014），与FEV1/FVC%水平呈正相关（r=0.402，P=0.01）。CRTH2（r=0.166、r=-0.040）、CysLT1R（r=0.114、r=-0.150）及H1R（r=0.103、r=-0.096）与血清TIgE、FeNO无明显相关性。结论： CD3⁺CD56⁺NKT细胞可能在支气管哮喘发病过程中起重要作用，H1R在CD3⁺CD56⁺NKT细胞上可能不表达，CRTh2与CysLT1R在BA患者CD3⁺CD56⁺NKT细胞上表达减少可能会为临床精准诊疗提供依据。

Abstract:

Objective: To investigate chemoattractant receptor homologous molecule expressed on Th2 cells (CRTh2) , cysteinyl leukotriene 1 receptor (CysLT1R) and histamine 1 receptor (H1R) expression and clinical significance in peripheral blood CD3⁺CD56⁺ natural killer T cells (NKT) of patients with bronchial asthma (BA). Methods: The peripheral blood of BA patients (BA group, n=40) and healthy control group (HC group, n=38) in The First Affiliated Hospital of Jinzhou Medical University from September 2020 to September 2021 were collected, and flow cytometry was used to detect the BA group and HC group expression of CRTh2, CysLT1R and H1R on CD3⁺CD56⁺ labeled NKT cells in peripheral blood. At the same time, its correlation with serum total immunoglobulin E (TIgE) , fractional exhaled nitric oxide (FeNO) and lung function forced expiratory volume in the first second/forced vital capacity% (FEV1/FVC%) were analyzed. Results: The percentage of NKT cells in the peripheral blood of the BA group[22.50 (15.78, 29.20)] was lower than that in the HC group[27.90 (21.50, 32.45)] (P=0.024). And in the further comparison, the percentage of CD3⁺ lymphocytes in the BA group[70.05 (63.20, 78.45)] was lower than that in the HC group[73.70 (69.88, 79.38)] (P=0.035). The percentage of CysLT1R in the BA group[0.08 (0.05, 0.17)] was lower than that in the HC group[0.16 (0.10, 0.34)] (P=0.004). The percentages of CRTH2 and H1R in the BA group[1.12 (0.53, 1.88) ; 5.21 (1.41, 10.10)] were not significantly different from those in the HC group[1.17 (0.60, 4.25) ; 4.61 (1.42, 8.53)] (P=0.234; P=0.697). Additionally, for the further comparison of the mean fluorescence intensity (MFI) of CRTh2 and H1R, BA group[925.52 (623.50, 1 279.25)] CRTh2 MFI was lower than HC group[1 345.50 (891.00, 1 977.75)] (P=0.002) ; there was no significant difference in H1R MFI between BA group[769 (657.50, 975.00)] H1R MFI and HC group[835.00 (560.00, 959.25)] (P=0.834). CD3⁺CD56⁺NKT cells had no significant correlation with serum TIgE and FeNO (r=-0.052; r=0.014) , but was positively correlated with the level of FEV1/FVC% (r=0.402, P=0.01). CRTH2 (r=0.166, r=-0.040) , CysLT1R (r=0.114, r=-0.150) and H1R (r=0.103, r=-0.096) had no significant correlation with TIgE and FeNO. Conclusion: CD3⁺CD56⁺NKT cells may play an important role in the pathogenesis of bronchial asthma, H1R may not be expressed on CD3⁺CD56⁺NKT cells, and the decreased expression of CRTh2 and CysLT1R on CD3⁺CD56⁺NKT cells in BA patients may provide a basis for accurate clinical diagnosis and treatment.