Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases.

A relatively large number of protein tyrosine phosphatases (PTPs) are known to regulate signaling through the T cell receptor (TCR). Recent human genetics studies have shown that several of these PTPs are encoded by major autoimmunity genes. Here, we will focus on the lymphoid tyrosine phosphatase (LYP), a critical negative modulator of TCR signaling encoded by the PTPN22 gene. The functional analysis of autoimmune-associated PTPN22 genetic variants suggests that genetic variability of TCR signal transduction contributes to the pathogenesis of autoimmunity in humans.