Cited by 152T-cell and B-cell ImmunologyImmunodeficiency and Autoimmune DisordersSystemic Lupus Erythematosus Research

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The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy

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Crofford, Leslie J., Nyhoff, Lindsay E., Sheehan, Jonathan H., Kendall, Peggy L.·2016·Expert Review of Clinical Immunology

DOI 10.1586/1744666x.2016.1152888PMC PMC5070917

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Abstract

Bruton's tyrosine kinase (BTK) mediates B cell signaling and is also present in innate immune cells but not T cells. BTK propagates B cell receptor (BCR) responses to antigen-engagement as well as to stimulation via CD40, toll-like receptors (TLRs), Fc receptors (FCRs) and chemokine receptors. Importantly, BTK can modulate signaling, acting as a "rheostat" rather than an "on-off" switch; thus, overexpression leads to autoimmunity while decreased levels improve autoimmune disease outcomes. Autoreactive B cells depend upon BTK for survival to a greater degree than normal B cells, reflected as loss of autoantibodies with maintenance of total antibody levels when BTK is absent. This review describes contributions of BTK to immune tolerance, including studies testing BTK-inhibitors for treatment of autoimmune diseases.

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BindingDB Entry 50008819: Optimization of novel reversible Bruton's tyrosine kinase inhibitors identified using Tethering-fragment-based screens.
BindingDB (2021) · UC San Diego · doi:10.7270/q2tx3jsf
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BindingDB (2022) · UC San Diego · doi:10.7270/q2pn9966
BindingDB Entry 50018849: Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase for B-Cell Malignancies and Autoimmune Diseases.
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BindingDB Entry 50015643: Utilizing structure based drug design and metabolic soft spot identification to optimize the in vitro potency and in vivo pharmacokinetic properties leading to the discovery of novel reversible Bruton's tyrosine kinase inhibitors.
BindingDB (2023) · UC San Diego · doi:10.7270/q26h4ncz
BindingDB Entry 50008690: Aminopyrazole Carboxamide Bruton's Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning.
BindingDB (2021) · UC San Diego · doi:10.7270/q28g8q30
BindingDB Entry 50001110: Discovery of 3-morpholino-imidazole[1,5-a]pyrazine BTK inhibitors for rheumatoid arthritis.
BindingDB (2020) · UC San Diego · doi:10.7270/q2959m2w
BindingDB Entry 50012415: Small molecule approaches to treat autoimmune and inflammatory diseases (Part I): Kinase inhibitors.
BindingDB (2022) · UC San Diego · doi:10.7270/q21v5jnk
BindingDB Entry 50007714: Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as potent, selective and reversible Bruton's tyrosine kinase (BTK) inhibitors for the treatment of rheumatoid arthritis.
BindingDB (2021) · UC San Diego · doi:10.7270/q2pr80bx
BindingDB Entry 50019956: Discovery of orally active 1,4,5,6,8-pentaazaacenaphthylens as novel, selective, and potent covalent BTK inhibitors for the treatment of rheumatoid arthritis.
BindingDB (2024) · UC San Diego · doi:10.7270/q2z32433
BindingDB Entry 50015733: Discovery of Reversible Covalent Bruton's Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib).
BindingDB (2023) · UC San Diego · doi:10.7270/q2w099wg

Authors: Crofford, L. J., Nyhoff, L. E., Sheehan, J. H., & Kendall, P. L.
Affiliations: Vanderbilt University (US)
Corresponding author: Crofford, Leslie J.
ORCID: Crofford, Leslie J.
Nyhoff, Lindsay E.
Sheehan, Jonathan H.
Kendall, Peggy L.
Venue: Expert Review of Clinical Immunology
Publisher: Informa UK Limited
Published: 2016-03-04
Volume: 12
Issue: 7
Pages: 763-773
ISSN: 1744-666X (ISSN-L)
1744-8409
DOI: 10.1586/1744666x.2016.1152888
PMC: PMC5070917
OpenAlex: W2258682798
Cited by: 142
References: 136
Citations by year: 2026: 9 · 2025: 15 · 2024: 13 · 2023: 18 · 2022: 29 · 2021: 21 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 5 · 2016: 2
FWCI: 0.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Expert Review of Clinical Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (NIAMS R01 AR049010, NIDDK R01 DK84246)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords: Bruton's tyrosine kinase, autoimmunity, B cell signaling, B cell receptor signaling, CD40 signaling, Toll-like receptors, Fc receptors, chemokine receptors, autoreactive B cells, autoantibodies, immune tolerance, BTK inhibitors, autoimmune disease therapy
MeSH terms: Agammaglobulinaemia Tyrosine Kinase, Animals, Anti-Inflammatory Agents, Autoantibodies, Autoimmune Diseases, B-Lymphocytes, Humans, Immune Tolerance, Lymphocyte Activation, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Signal Transduction, Autoimmunity

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The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy

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