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自身免疫性疾病中树突状细胞激活T细胞的分子机制

Molecular Mechanisms of T Cells Activation by Dendritic Cells in Autoimmune Diseases.

作者信息

Tai Yu, Wang Qingtong, Korner Heinrich, Zhang Lingling, Wei Wei

机构信息

Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.

Menzies Institute for Medical Research, Hobart, TAS, Australia.

出版信息

Front Pharmacol. 2018 Jun 26;9:642. doi: 10.3389/fphar.2018.00642. eCollection 2018.

Abstract

The interaction between T cell and dendritic cells (DCs) that leads to T cell activation affects the progression of the immune response including autoimmune diseases. Antigen presentation on immune cell surface, formation of an immunological synapse (IS), and specific identification of complex by T cells including two activating signals are necessary steps that lead to T cell activation. The formation of stimulatory IS involves the inclusion of costimulatory molecules, such as ICAM-1/LFA-1 and CD28/B7-1, and so on. Some fusion proteins and monoclonal antibodies targeting costimulatory molecules have been developed and approved to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (T1D), inflammatory bowel disease (IBD), and psoriasis. These biological agents, including CTLA-4- and LFA-3-Ig, anti-CD3 monoclonal antibody, could prevent the successful engagement of DCs by T cell with significant efficacy and safety profile. In this article, we reviewed the molecular mechanisms of T cell activation during the interaction between T cells and DCs, and summarized some biological agents that target costimulatory molecules involved in the regulation of T cell activation.

摘要

导致T细胞活化的T细胞与树突状细胞(DC)之间的相互作用会影响包括自身免疫性疾病在内的免疫反应进程。免疫细胞表面的抗原呈递、免疫突触(IS)的形成以及T细胞对包括两个激活信号在内的复合物的特异性识别是导致T细胞活化的必要步骤。刺激性IS的形成涉及共刺激分子的参与,如细胞间黏附分子-1/淋巴细胞功能相关抗原-1(ICAM-1/LFA-1)和CD28/B7-1等。一些靶向共刺激分子的融合蛋白和单克隆抗体已被开发并获批用于治疗自身免疫性疾病,包括类风湿关节炎(RA)、系统性红斑狼疮(SLE)、多发性硬化症(MS)、I型糖尿病(T1D)、炎症性肠病(IBD)和银屑病。这些生物制剂,包括细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和淋巴细胞功能相关抗原3(LFA-3)-免疫球蛋白(Ig)、抗CD3单克隆抗体,能够有效且安全地阻止T细胞与DC的成功结合。在本文中,我们综述了T细胞与DC相互作用过程中T细胞活化的分子机制,并总结了一些靶向参与T细胞活化调节的共刺激分子的生物制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4383/6028573/92b614dd0a08/fphar-09-00642-g001.jpg

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