转PD-L1人脐带间充质干细胞联合地塞米松治疗CIA小鼠模型的研究  

Therapeutic effects of PD-L1-transfecting HUCMSCs combined with dexamethasone in the treatment of mouse with collagen induced arthritis

作　　者：胡琼英[1] 赵沙沙[1] 艾承锦[1] 陈高莉 熊大迁[1] HU Qiongying;ZHAO Shasha;AI Chengjin;CHEN Gaoli;XIONG Daqian(Department of Laboratory Medicine,Teaching Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China)

机构地区：[1]成都中医药大学附属医院检验科,610072

出　　处：《免疫学杂志》2020年第4期325-330,共6页Immunological Journal

基　　金：国家自然科学基金(81601835);四川省科技厅面上项目(18YYJC0689);四川省卫生计生委课题(18ZD039)。

摘　　要：目的探讨转程序性死亡分子配体(programmed death-ligand 1,PD-L1)人脐带间充质干细胞(human umbilical mesenchymal stem cells,HUMSCs)联合糖皮质激素类药物(GCs)地塞米松(dexamethasone,DXM)在体内对类风湿关节炎(rheumatoid arthritis,RA)的作用效果,为RA的治疗提供新的思路。方法构建PD-L1基因(CD274)克隆并包装病毒,再高效感染人脐带间充质干细胞(PD-L1+HUCMSC),表达PD-L1蛋白;建立胶原诱导类风湿关节炎(collagen induced arthritis,CIA)小鼠模型,并用PD-L1+HUCMSC联合DXM(0.5 mg/kg)(PD-L1-HUCMSCs/DXM)进行治疗,监测小鼠的体质量和临床评分变化;检测相关免疫细胞的变化及炎症相关因子的表达情况。结果PD-L1-HUCMSCs/DXM可减轻CIA小鼠关节发病程度(P<0.05);显著降低淋巴结和脾脏中活化T细胞和B细胞的数量(P<0.05),显著增加调节性T细胞(Treg)和调节性B细胞(Breg)数量(P<0.05);抑制小鼠体内促炎因子、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素1β(interleukin-1β,IL-1β)、IL-6、IL-17和IL-10的生成(P<0.05)。结论转PD-L1人脐带间充质干细胞联合地塞米松可减轻和缓解RA的临床症状,抑制其发生和发展,为研究和治疗RA提供了新思路。This study was designed to investigate the therapeutic effects on rheumatoid arthritis(RA)with the treatment of programmed death-ligand 1(PD-L1)transfecting human umbilical mesenchymal stem cells(HUCMSCs)combined with dexamethasone(PD-L1-HUCMSCs/DXM),and supply a new evidence for RA treatment.A collageninduced arthritis(CIA)mouse model was constructed,and injected with PD-L1-HUCMSCs/DXM(0.5 mg/kg)continuously through abdominal cavity.Then,the body weight and joint clinical score changing of mice were monitored and recorded.Finally,we analyzed the changing of mouse’s immune cells and inflammatory cytokines.As the results showed that PD-L1-HUCMSCs/DXM could alleviate mouse joint pathology status and reduce the number of T cells,activated T cells and activated B cells in lymph nodes and spleen significantly(P<0.05),increase the number of regulatory T cells(Treg)and regulatory B cells(Breg)in lymph nodes and spleen significantly(P<0.05).Moreover,PD-L1-HUCMSCs/DXM inhibited the production of tumor necrosis factor-α,interleukin-1β,IL-6,IL-17 and IL-10.In conclusion,PD-L1-HUCMSCs/DXM alleviates RA clinical symptom and inhibits RA development,which provides a novel idea to study and treat RA.

关 键 词：类风湿关节炎 程序性死亡分子配体 人脐带间充质干细胞 地塞米松 

分 类 号：R392.9[医药卫生—免疫学]