抗CD23抗体在变应性鼻炎大鼠中介导Bregs分泌IL-10调节T细胞的活化  

CD23 on B cells determines Breg-facilitated IL-10 secretion as well as activation of T cells

作　　者：陈琦[1] 巴云鹏[1] 周明辉[1] 李素丹 张普文 CHEN Qi;BA Yunpeng;ZHOU Minghui;LI Sudan;ZHANG Puwen(Department of Rhinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000,Chin)

机构地区：[1]郑州大学第一附属医院鼻科,郑州450000

出　　处：《临床耳鼻咽喉头颈外科杂志》2018年第12期931-937,共7页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

摘　　要：目的:探寻抗CD23抗体是否通过Bregs介导的IL-10分泌调节T细胞的活化,寻找治疗变应性鼻炎的新靶点。方法:建立变应性鼻炎大鼠模型,应用抗CD23抗体干预,观察大鼠的行为学改变,通过皮肤被动过敏原实验、酶联免疫吸附实验、苏木精-伊红染色、免疫荧光、流式细胞术了解血清学指标、全身及鼻腔局部黏膜情况。结果:与正常对照组相比,变应性鼻炎组大鼠出现喷嚏、挠鼻、流涕,皮下肿块增大;血液中IL-10水平、IFN-γ、调节性B细胞(Bregs)百分率降低,IL-4水平、CD23^+B细胞、CD4^+T细胞百分率增高;鼻黏膜CD23荧光强度增加,CD19和IL-10荧光强度减弱。与变应性鼻炎组相比,抗体干预组大鼠喷嚏次数、挠鼻次数、流涕症状明显改善,皮下肿块缩小;血液中IL-10水平、IFN-γ、全血中Bregs细胞百分率增高,IL-4水平、CD23^+B细胞、CD4^+T细胞百分率降低;鼻黏膜CD23荧光强度减弱,CD19和IL-10荧光强度增强。两种给药途径差异无统计学意义。结论:B细胞上CD23表达增强参与变应性鼻炎的发生发展;抗CD23抗体应用可调控变应鼻炎的症状和体征,鼻腔滴入可作为抗CD23抗体应用的首选方法,抗CD23有望成为控制和治疗变应性鼻炎的新方法。抗CD23抗体可通过依赖Bregs分泌IL-10介导的T细胞活化发挥治疗作用。Objective：To explore whether or not the IL-10 mediated by Bregs modulate the secreting T cells activation by the anti-CD23 antibody,to find a new target for the treatment of allergic rhinitis.Method：The rat model of allergic rhinitis was established.Anti-CD23 antibody was used to observe the behavioral changes,passive skin allergen test,enzyme-linked immunosorbent assay,hematoxylin and eosin staining,immunofluorescence and flow cytometry serological indicators,systemic and nasal mucosa.Result：Compared with the blank control group,allergic rhinitis group rats sneezing,flexible nose,runny nose,subcutaneous mass increases;The levels of IL-10,IFN-γand Bregs in blood decreased,the levels of IL-4,CD23＋B cells and CD4＋T cells increased;Nasal mucosa CD23 fluorescence intensity increased,CD19 and IL-10 fluorescence intensity decreased.Compared with the allergic rhinitis group,the number of sneezing,the frequency of nasal flexion,the symptoms of runny nose and the subcutaneous mass in the antibody intervention group were significantly improved;The levels of IL-10 in the blood,IFN-γ,the percentage of Bregs cells in whole blood increased,the levels of IL-4,CD23＋B cells and CD4＋T cells decreased;Nasal mucosa CD23 fluorescence intensity decreased,CD19 and IL-10 fluorescence intensity increased.There is little difference between the two routes of administration.Conclusion：The enhanced expression of CD23 on B cells is involved in the development of allergic rhinitis.The anti-CD23 antibody may control the symptoms and signs of allergic rhinitis.There is no significant difference between subcutaneous administration and improved nasal-drip way.As the preferred method of anti-CD23 antibody application,anti-CD23 is expected to become a new method to control and treat allergic rhinitis.Anti-CD23 antibodies can exert a therapeutic effect by T cell activation,which rely on the Bregs-mediated secretion of IL-10.

关 键 词：鼻炎 变应性 CD23 白细胞介素10 调节性B细胞 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]