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布鲁顿酪氨酸激酶抑制在中枢神经系统中的免疫调节功能

The Immunomodulatory Functions of BTK Inhibition in the Central Nervous System.

作者信息

Cao Tingyu, Wang Zengguang, Zhu Xiaodong

机构信息

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

出版信息

J Inflamm Res. 2022 Nov 24;15:6427-6438. doi: 10.2147/JIR.S389958. eCollection 2022.

Abstract

Bruton's tyrosine kinase (BTK) is a central signaling node in B cells. BTK inhibition has witnessed great success in the treatment of B-cell malignancies. Additionally, in the immune system, BTK is also a prominent component linking a wide variety of immune-related pathways. Therefore, more and more studies attempting to dissect the role of BTK in autoimmune and inflammation progression have emerged in recent years. In particular, BTK expression was also found to be elevated within the central nervous system (CNS) during neuroinflammation. BTK inhibitors are capable of crossing the blood-brain barrier rapidly to modulate B cell functions, attenuate microglial activities and affect NLRP3 inflammasome pathways within the CNS to improve the outcome of diseases. Thus, BTK inhibition appears to be a promising approach to modulate dysregulated inflammation in the CNS and alleviate destruction caused by excessive inflammatory responses. This review will summarize the immunomodulatory mechanisms in which BTK is involved in the development of neurological diseases and discuss the therapeutic potential of BTK inhibition for the treatment of neuroinflammatory pathology.

摘要

布鲁顿酪氨酸激酶(BTK)是B细胞中的核心信号节点。BTK抑制在B细胞恶性肿瘤治疗中取得了巨大成功。此外,在免疫系统中,BTK也是连接多种免疫相关途径的重要组成部分。因此,近年来出现了越来越多试图剖析BTK在自身免疫和炎症进展中作用的研究。特别是,在神经炎症期间,中枢神经系统(CNS)内的BTK表达也被发现升高。BTK抑制剂能够迅速穿过血脑屏障,调节B细胞功能,减弱小胶质细胞活性,并影响中枢神经系统内的NLRP3炎性小体途径,从而改善疾病结局。因此,抑制BTK似乎是一种有前景的方法,可调节中枢神经系统中失调的炎症,并减轻过度炎症反应造成的破坏。本综述将总结BTK参与神经疾病发展的免疫调节机制,并讨论抑制BTK治疗神经炎性病理的治疗潜力。

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