Regulation of T cell receptor (TCR) signaling by tyrosine phosphatases: Recent advances and implication for therapeutic approach in autoimmune diseases.

The effector function of T cells is critical for regulation of the initiation and progression of autoimmune diseases; whereas the T cell activation and homeostasis are tightly controlled by signals from T cell receptor (TCR). The early TCR signaling pathways are dependent on rapid phosphorylation and dephosphorylation of multiple signaling proteins in the TCR complex. These processes are tightly regulated by the interplay between protein kinases and phosphatases, leading to T cell activation. Genetic polymorphisms of these kinases or phosphatases have been linked to an increased susceptibility to autoimmune disorders in humans. Mice with deficiencies in these corresponding genes often exhibit T cell hyper-reactivity and autoimmune phenotypes in animal models. Tyrosine phosphatases have been demonstrated to alter T cell fate by negatively regulating early TCR signaling. Therefore, the tyrosine phosphatases that regulate TCR signaling are emerging as potential therapeutic targets to modulate T cell responses for the treatment of autoimmune diseases. In this review, we provide an overview of the current progress and perspectives of tyrosine phosphatases that regulate TCR signaling in T cell activation, and their potential as therapeutic targets for autoimmune diseases.