title: The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy.
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.
authors: a Division of Rheumatology & Immunology, Department of Medicine , Vanderbilt University , Nashville , TN , USA.|b Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , TN , USA.
authors: Leslie J
authors: LJ
authors: Crofford
authors: b Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , TN , USA.
authors: Lindsay E
authors: LE
authors: Nyhoff
authors: c Center for Structural Biology, Department of Biochemistry , Vanderbilt University , Nashville , TN , USA.
authors: Jonathan H
authors: JH
authors: Sheehan
authors: b Department of Pathology, Microbiology & Immunology , Vanderbilt University , Nashville , TN , USA.|d Division of Allergy, Pulmonary and Critical Care, Department of Medicine , Vanderbilt University , Nashville , TN , USA.
authors: Peggy L
authors: PL
authors: Kendall
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001323:Autoantibodies / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: B lymphocyte signaling; BTK inhibitors; Bruton’s tyrosine kinase; autoimmune inflammatory arthritis; autoimmunity; systemic lupus erythematosus; type 1 diabetes