Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity

More than half of the known protein tyrosine phosphatases (PTPs) in the human genome are expressed in T cells, and significant progress has been made in elucidating the biology of these enzymes in T-cell development and function. Here we provide a systematic review of the current understanding of the roles of PTPs in T-cell activation, providing insight into their mechanisms of action and regulation in T-cell receptor signalling, the phenotypes of their genetically modified mice, and their possible involvement in T-cell-mediated autoimmune disease. Our projection is that the interest in PTPs as mediators of T-cell homeostasis will continue to rise with further functional analysis of these proteins, and PTPs will be increasingly considered as targets of immunomodulatory therapies.