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The role of Bruton's tyrosine kinase in the immune system and disease
Immunology ( IF 6.4 ) Pub Date : 2021-09-17 , DOI: 10.1111/imm.13416
Charlotte McDonald 1 , Charalampos Xanthopoulos 1 , Efterpi Kostareli 1
Affiliation  

Bruton's tyrosine kinase (BTK) is a TEC kinase with a multifaceted role in B-cell biology and function, highlighted by its position as a critical component of the B-cell receptor signalling pathway. Due to its role as a therapeutic target in several haematological malignancies including chronic lymphocytic leukaemia, BTK has been gaining tremendous momentum in recent years. Within the immune system, BTK plays a part in numerous pathways and cells beyond B cells (i.e. T cells, macrophages). Not surprisingly, BTK has been elucidated to be a driving factor not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. To extort this role, BTK inhibitors such as ibrutinib have been developed to target BTK in other diseases. However, due to rising levels of resistance, the urgency to develop new inhibitors with alternative modes of targeting BTK is high. To meet this demand, an expanding list of BTK inhibitors is currently being trialled. In this review, we synopsize recent discoveries regarding BTK and its role within different immune cells and pathways. Additionally, we discuss the broad significance and relevance of BTK for various diseases ranging from haematology and rheumatology to the COVID-19 pandemic. Overall, BTK signalling and its targetable nature have emerged as immensely important for a wide range of clinical applications. The development of novel, more specific and less toxic BTK inhibitors could be revolutionary for a significant number of diseases with yet unmet treatment needs.

中文翻译:

布鲁顿酪氨酸激酶在免疫系统和疾病中的作用

布鲁顿酪氨酸激酶 (BTK) 是一种 TEC 激酶,在 B 细胞生物学和功能中具有多方面的作用,特别是其作为 B 细胞受体信号传导通路的关键组成部分的地位。由于其作为包括慢性淋巴细胞白血病在内的多种血液恶性肿瘤的治疗靶点的作用,BTK 近年来获得了巨大的发展势头。在免疫系统中,BTK 在 B 细胞以外的许多途径和细胞(即 T 细胞、巨噬细胞)中发挥作用。毫不奇怪,BT​​K 已被阐明不仅是淋巴增殖性疾病的驱动因素,而且也是自身免疫性疾病和感染反应的驱动因素。为了发挥这一作用,已经开发了依鲁替尼等 BTK 抑制剂来针对其他疾病的 BTK。然而,由于耐药性水平不断上升,开发具有替代 BTK 靶向模式的新抑制剂的紧迫性很高。为了满足这一需求,目前正在试验越来越多的 BTK 抑制剂。在这篇综述中,我们总结了有关 BTK 及其在不同免疫细胞和途径中的作用的最新发现。此外,我们还讨论了 BTK 对从血液学、风湿病学到 COVID-19 大流行等各种疾病的广泛意义和相关性。总体而言,BTK 信号传导及其可靶向性对于广泛的临床应用来说非常重要。新型、特异性更强、毒性更小的 BTK 抑制剂的开发对于许多治疗需求尚未得到满足的疾病来说可能是革命性的。
更新日期:2021-11-04
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