Regulation of T Cell Signaling and Immune Responses by PTPN22

Protein tyrosine phosphatases (PTPs) play central roles in the regulation of cell signaling, organismal development, cellular differentiation and proliferation, and cancer. In the immune system, PTPs regulate the activation, differentiation and effector function of lymphocytes and myeloid cells whilst single-nucleotide polymorphisms (SNPs) in PTP-encoding genes have been identified as risk factors for the development of autoimmunity. In this review we describe the roles for PTP nonreceptor type 22 (PTPN22) in the regulation of T lymphocyte signaling and activation in autoimmunity, infection and cancer. We summarize recent progress in our understanding of the regulation of PTPN22 activity, the impact of autoimmune disease-associated PTPN22 SNPs on T cell responses and describe approaches to harness PTPN22 as a target to improve T cell-based immunotherapies in cancer.