Non-receptor tyrosine kinase signaling in autoimmunity and therapeutic implications

Abstract

Autoimmune diseases are characterized by impaired immune tolerance towards self-antigens, leading to enhanced immunity to self by dysfunctional B cells and/or T cells. The activation of these cells is controlled by non-receptor tyrosine kinases (NRTKs), which are critical mediators of antigen receptor and cytokine receptor signaling pathways. NRTKs transduce, amplify and sustain activating signals that contribute to autoimmunity, and are counter-regulated by protein tyrosine phosphatases (PTPs). The function of and interaction between NRTKs and PTPs during the development of autoimmunity could be key points of therapeutic interference against autoimmune diseases. In this review, we summarize the current state of knowledge of the functions of NRTKs and PTPs involved in B cell receptor (BCR), T cell receptor (TCR), and cytokine receptor signaling pathways that contribute to autoimmunity, and discuss their targeting for therapeutic approaches against autoimmune diseases.

Keywords: Autoantibodies; Autoimmunity; Effector T cells; Kinase Inhibitors; Non-receptor tyrosine kinase; Protein Tyrosine Phosphatase.