Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies

Stefan F.H. Neys, Rudi W. Hendriks*, Odilia B.J. Corneth

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

12 Citations (Scopus)
9 Downloads (Pure)

Abstract

Bruton’s tyrosine kinase (BTK) was discovered due to its importance in B cell development, and it has a critical role in signal transduction downstream of the B cell receptor (BCR). Targeting of BTK with small molecule inhibitors has proven to be efficacious in several B cell malignancies. Interestingly, recent studies reveal increased BTK protein expression in circulating resting B cells of patients with systemic autoimmune disease (AID) compared with healthy controls. Moreover, BTK phosphorylation following BCR stimulation in vitro was enhanced. In addition to its role in BCR signaling, BTK is involved in many other pathways, including pattern recognition, Fc, and chemokine receptor signaling in B cells and myeloid cells. This broad involvement in several immunological pathways provides a rationale for the targeting of BTK in the context of inflammatory and systemic AID. Accordingly, numerous in vitro and in vivo preclinical studies support the potential of BTK targeting in these conditions. Efficacy of BTK inhibitors in various inflammatory and AID has been demonstrated or is currently evaluated in clinical trials. In addition, very recent reports suggest that BTK inhibition may be effective as immunosuppressive therapy to diminish pulmonary hyperinflammation in coronavirus disease 2019 (COVID-19). Here, we review BTK’s function in key signaling pathways in B cells and myeloid cells. Further, we discuss recent advances in targeting BTK in inflammatory and autoimmune pathologies.

Original languageEnglish
Article number668131
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
Publication statusPublished - 4 Jun 2021

Bibliographical note

Funding Information:
This project was funded by grants from the Target2B consortium, Erasmus MC MRace, and the Dutch Arthritis Association.

Publisher Copyright:
© Copyright © 2021 Neys, Hendriks and Corneth.

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