免疫共刺激分子与自身免疫性疾病的研究进展  

Relationship Between Immune Checkpoint and Autoimmune Disease

作　　者：冉庆森[1] 李琦[1] 刘丽[1] 孙立东 杨庆[1] 李玉洁[1] 陈颖[1] 王娅杰[1] 翁小刚[1] 蔡维艳[1] 朱晓新[1] RAN Qing-sen;LI Qi;LIU Li;SUN Li-dong;YANG Qing;LI Yu-jie;CHEN Ying;WANG Ya-jie;WENG Xiao-gang;CAI Wei-yan;ZHU Xiao-xin(Institute of Chinese Materia Medica,China A cade my of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所,北京100700

出　　处：《中国实验方剂学杂志》2020年第18期188-195,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2017ZX09101002-002-002);中国中医科学院“一带一路”国际合作专项(GH201914);中国中医科学院院内课题(ZXKT17010,Z20107019-03,ZZ13-YQ-044)。

摘　　要：正常机体的免疫系统具有区别"自己"和"非己"的能力,对非己抗原能够发生免疫应答,对自身抗原则是处于无应答或微弱应答状态,时刻处于"免疫激活-免疫耐受"的动态平衡状态。然而,如果正常的免疫耐受被打破,将"自己"识别成"非己",处于非正常免疫激活状态的T细胞就会持续迁延的对自身抗原产生异常的免疫应答,结果会导致自身免疫性疾病(ADS)的发生。因此,"无效"的免疫识别和免疫应答成为自身免疫性疾病的发病的主要致病机制。免疫共刺激分子(co-stimulatory molecule)作为连接抗原递呈细胞(APC)和免疫细胞(T细胞,B细胞)的重要纽带,有研究已经证实,正性免疫共刺激分子的高表达和负性免疫共刺激分子的低表达都会导致自身免疫耐受的缺陷,进而引发自身免疫性疾病。依据中医药"纠偏","扶正"的治疗特色。本文通过对4种典型性的自身免疫性疾病:系统性则是以红斑狼疮(SLE)和类风湿性关节炎(RA)为代表;器官特异性则是以多发性硬化症(MS)和Ⅰ型糖尿病(T1DM)发病机制进行探讨,依赖于这4种疾病发病过程中免疫共刺激分子对免疫识别与免疫应答的重要影响,并且依托于中医药对自身免疫平衡调节的作用,结合近十年来的相关文献,对免疫共刺激分子与自身免疫性疾病之间的关系进行论述,探寻不同的免疫共刺激分子在不同的自身免疫病中的共性,并初探中药以PD1-PDL1为药物靶点治疗自身免疫病的可行性。The normal immune system has the ability to distinguish between"self"and"non-self".Because of its dynamic balance of"immune activity-immune tolerance",it will produce immune response to the non-self antigen,but with no response or weak response to the self-antigen.However,if the balance was broken,T cell in the abnormal immune activation state will respond continually to the self-antigen,with an abnormal immune response,which caused autoimmune disease.Pathologically,"invalid"immune recognition and immune response become the main causes for autoimmune diseases.Co-stimulatory molecule is an important link between Attach antigen presenting cells(APC)and immune cells(T cell and B cell).Studies have proved that excessive co-stimulation and/or insufficient co-inhibition could cause detect of self-tolerance and induce autoimmunity.Although co-stimulatory and co-inhibitory pathways have a significant impact on all ADS,this paper focuses on their effect on two systemic autoimmune diseases[systemic lupus erythematosus(SLE)and rheumatoid arthritis(RA)]and two organ-specific autoimmune diseases[multiple sclerosis(MS)and type 1 diabetes(T1 DM)],in order to discuss the pathogenesis and relationship between co-stimulatory molecules and autoimmune diseases.

关 键 词：免疫平衡 免疫共刺激分子 自身免疫病 

分 类 号：R2-0[医药卫生—中医学] R22