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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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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