TNFR2对CD4^(+)Foxp3^(+)Treg的活化、增殖及功能影响的研究进展  

Research progress on the decisive role of TNFR2 in the activation,proliferative expansion,and function of CD4^(+)Foxp3^(+)Tregs

作　　者：郑静彬 杨阳 陈新[1] ZHENG Jing-bin;YANG Yang;CHEN Xin(State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao 999078,China)

机构地区：[1]澳门大学中华医药研究院中药质量研究国家重点实验室,中国澳门999078

出　　处：《现代免疫学》2022年第1期1-6,71,共7页Current Immunology

基　　金：澳门大学研究经费资助项目(MYRG2016-00023-ICMS-QRCM,MYRG2017-00120-ICMS,MYRG2019-00169-ICMS);澳门科技发展基金会(FDCT)科研经费资助项目(201/2017/A3,0056/2019/AFJ)。

摘　　要：CD4^(+)Foxp3^(+)Treg是调节免疫稳态所必需的一群免疫细胞。Treg数量和功能的异常与多种疾病的发生有关,包括自身免疫性疾病、过敏性疾病、移植排斥反应和肿瘤免疫逃逸等。TNF-α在炎症和免疫反应中有着双重作用,即促进炎症反应和介导免疫耐受。这很可能与其2个受体——肿瘤坏死因子受体(tumor necrosis factor receptor,TNFR)1和TNFR2独特的信号转导有关。TNFR1几乎在所有类型的细胞中普遍表达,而TNFR2的表达分布则较为局限。现在越来越多的证据表明,Treg较特异性地表达高水平TNFR2。更重要的是,TNFR2在Treg活化、增殖、功能和表型稳定中均起决定性作用。同时,TNFR2参与Treg分化、发育、免疫功能发挥等生理过程。深入研究TNFR2信号活化Treg的分子机制,可为自身免疫性疾病、过敏性疾病、移植物抗宿主病(graft-versus-host disease,GVHD)和恶性肿瘤等疾病的治疗提供进一步的帮助。该文主要介绍TNF-TNFR信号的分子基础和信号转导途径,分析和讨论TNF-TNFR2信号对Treg活化、增殖及功能的影响及其分子机制的最新研究进展。As professional immune cells,CD4^(+) Foxp3^(+) Tregs play an indispensable role in the maintenance of immune homeostasis.The abnormal number or function of Tregs is attributable to the pathogenesis of autoimmune disease,allergy,allograft rejection,and tumor immune evasion.TNF-α is a pleiotropic cytokine with both proinflammatory and immunosuppressive effects,which is presumably mediated by the unique signal transduction of two receptors,tumor necrosis factor receptor(TNFR)1 and TNFR2.TNFR1 is expressed by almost all types of cells,while the expression of TNFR2 is relatively limited.It is known that TNFR2 is preferentially expressed by Tregs.There is compelling evidence that TNFR2 plays a decisive role in the activation,proliferative expansion,function,and phenotypic stability of Tregs.Furthermore,TNFR2 is involved in the differentiation and development of Tregs.Thorough understanding molecular mechanism of TNFR2 signaling events required for the activation of Tregs can help to create more effective treatments of autoimmune disease,allergy,allograft rejection,graft-versus-host disease(GVHD),and cancer.This review introduces the current understanding of the molecular basis and TNF-TNFRs signaling transduction pathways;analyzes the latest research on the decisive role of TNF-TNFR2 interaction in the activation,proliferative expansion,and function of Tregs as well as its molecular mechanism.

关 键 词：肿瘤坏死因子 CD4^(+)Foxp3^(+)调节性T细胞 肿瘤坏死因子受体2 自身免疫性疾病 肿瘤 

分 类 号：R392.1[医药卫生—免疫学]