TY - JOUR
T1 - The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy
AU - Crofford, Leslie J.
AU - Nyhoff, Lindsay E.
AU - Sheehan, Jonathan H.
AU - Kendall, Peggy L.
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/7/2
Y1 - 2016/7/2
N2 - 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.
AB - 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.
KW - B lymphocyte signaling
KW - BTK inhibitors
KW - Bruton’s tyrosine kinase
KW - autoimmune inflammatory arthritis
KW - autoimmunity
KW - systemic lupus erythematosus
KW - type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84962490021&partnerID=8YFLogxK
U2 - 10.1586/1744666X.2016.1152888
DO - 10.1586/1744666X.2016.1152888
M3 - Review article
C2 - 26864273
AN - SCOPUS:84962490021
SN - 1744-666X
VL - 12
SP - 763
EP - 773
JO - Expert Review of Clinical Immunology
JF - Expert Review of Clinical Immunology
IS - 7
ER -