The Role of Bruton's Tyrosine Kinase in Autoimmunity and Implications for Therapy

Overview

Journal Expert Rev Clin Immunol

Specialty Allergy & Immunology

Date 2016 Feb 12

PMID 26864273

Citations 64

Authors

Leslie J Crofford

Lindsay E Nyhoff

Jonathan H Sheehan

Peggy L Kendall

Affiliations

Soon will be listed here.

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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