趋化因子受体6在过敏性鼻炎外周血和鼻黏膜中的表达及意义

Expression and significance of CCR6 in regulatory T cells and eosinophils in allergic rhinitis

背景近年来,研究表明趋化因子受体6(chemokine receptor 6,CCR6)可能与过敏性疾病中免疫细胞的募集有关,但CCR6在过敏性鼻炎(allergic rhinitis,AR)中的作用尚不明确。目的检测AR患者外周血中Treg表面CCR6表达情况和AR小鼠鼻黏膜中CCR6的分布和表达,探究CCR6在AR中趋化募集免疫细胞的作用机制。方法留取AR患者和健康人群(HC组)的外周静脉血样本,流式细胞仪检测并比较Treg所占比例及其表面CCR6的表达情况。制备AR小鼠模型,苏木精和伊红染色观察AR小鼠和对照组小鼠鼻黏膜嗜酸性粒细胞浸润情况,免疫组织化学染色检测鼻黏膜中CCR6蛋白的表达。结果AR患者外周血CD4^(+)CD25^(+)FoxP3^(+)Treg细胞占比(2.92%±1.83%vs 5.23%±2.58%)和CCR6阳性细胞占比(30.02%±11.50%vs 50.20%±11.67%)较HC组明显降低(P均<0.01),AR患者CCR6与Treg细胞呈正相关(r=0.889,P<0.01)。小鼠AR模型组鼻黏膜中嗜酸性粒细胞数[24.0(14.5,31.5)vs 0(0,1.8)]和CCR6阳性细胞数量(136.25±26.04 vs81.00±23.08)较对照组明显增多(P均<0.01),CCR6表达与嗜酸性粒细胞数呈正相关(r=0.766,P<0.01)。结论CCR6在AR外周血和鼻黏膜中的变化提示CCR6参与AR发病过程,可能与诱导免疫细胞趋化聚集有关。

Background In recent years,many studies have shown that chemokine receptor 6(CCR6)may be involved in the recruitment of immune cells in allergic diseases,but the role of CCR6 in allergic rhinitis(AR)remains unclear.Objective To detect the expression of CCR6 on Treg surface in peripheral blood of AR patients and the distribution and expression of CCR6 on nasal mucosa of AR mice,and explore the mechanism of CCR6 chemotactic recruitment of immune cells in AR.Methods Peripheral blood samples from allergic rhinitis patients and healthy people were collected,and the proportion of Treg and the expression of CCR6 on its surface were detected by flow cytometry.Then AR mouse model was established,hematoxylin and eosin staining was used to observe eosinophil infiltration in nasal mucosa of AR mice and control mice,and immunohistochemical staining was used to detect the expression of CCR6 protein in nasal mucosa.Results The proportion of CD4^(+)CD25^(+)FoxP3^(+)Treg([2.92±1.83]%vs[5.23±2.58]%)and CCR6^(+)Treg([30.02±11.50]%vs[50.20±11.67]%)in the AR patients were significantly lower than those in the HC group(P<0.01,respectively),and there was a positive correlation between CD4^(+)CD25^(+)FoxP3^(+)Treg and CCR6 in the peripheral blood of the AR patients(r=0.889,P<0.01).The number of eosinophils[24.0(14.5,31.5)vs 0(0,1.8)]and cells expressing CCR6([136.25±26.04]vs[81.00±23.08])in the AR group was significantly higher than that in the control group(P<0.01,respectively),and there was a positive correlation between eosinophils and cells expressing CCR6 in the nasal mucosa of AR mice(r=0.766,P<0.01).Conclusion The changes of CCR6 in AR peripheral blood and nasal mucosa suggest that CCR6 is involved in the pathogenesis of AR and may be related to the induction of chemotaxis of immune cells.