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ISSN 打印: 1040-8401
ISSN 在线: 2162-6472

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DOI: 10.1615/CritRevImmunol.2018025184
pages 17-62

The Role of Bruton's Tyrosine Kinase in Immune Cell Signaling and Systemic Autoimmunity

Jasper Rip
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, the Netherlands
Esmee K. Van Der Ploeg
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, the Netherlands
Rudi W. Hendriks
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, the Netherlands
Odilia B. J. Corneth
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, the Netherlands

ABSTRACT

Bruton's tyrosine kinase (BTK) is an intracellular signaling molecule first identified as the molecule affected in X-linked agammaglobulinemia (XLA) patients, who almost completely lack peripheral B cells and serum immunoglobulins. BTK is crucial for B cell development and various B cell functions, including cytokine and natural antibody production. Importantly, it is also expressed in numerous other cells, including monocytes, macrophages, granulocytes, dendritic cells, and osteoclasts. A few rare cases of autoimmune disease in XLA patients have been described. Interestingly, increased BTK protein expression in patients with systemic autoimmune disease appears to be correlated with autoantibody production. In addition, BTK may promote autoimmunity as an important driver of an imbalance in B-T cell interaction. Because of this overwhelming evidence of a pathogenic role of BTK in autoimmunity, several clinical trials in rheumatoid arthritis and systemic lupus erythematosus patients with BTK inhibitors are currently running. Here, we review BTK function in different signaling pathways and in different cell lineages, focusing on the growing body of literature indicating a critical role for BTK in autoimmunity. We also discuss BTK and the promising results of BTK inhibition in animal models of autoimmune disease.


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