4.6 Review

The role of Bruton's tyrosine kinase in the immune system and disease

Journal

IMMUNOLOGY
Volume 164, Issue 4, Pages 722-736

Publisher

WILEY
DOI: 10.1111/imm.13416

Keywords

autoimmunity; Bruton's tyrosine kinase; BTK inhibitor; chronic lymphocytic leukaemia; ibrutinib; infections; lymphoproliferative disorders

Categories

Funding

  1. Academy of Medical Sciences, Springboard Programme
  2. Leukaemia and Lymphoma NI Funding [SBF005\1113, R2740CEM]
  3. Department of Economy (DfE, N. Ireland)

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BTK, a TEC kinase with a critical role in B-cell biology, has gained momentum as a therapeutic target in various hematological malignancies. It plays a significant role not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. Developing novel, more specific BTK inhibitors is crucial to address the rising levels of resistance and meet the unmet treatment needs of various diseases.
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.

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