The role of PTPN22 in autoimmunity: learning from mice.

Protein tyrosine phosphatase nonreceptor 22 (PTPN22) represents a strong susceptibility gene which is shared by many autoimmune diseases. Exploring the mechanism behind this association could help to understand their pathogenesis as well as to identify novel therapeutical targets. Recently, multiple mouse models including knock-out, knock-in, knock-down and transgenic mice were generated to delineate PTPN22s function in this context. Depending on the genetic background, mouse PTPN22_619W mutation results in spontaneous autoimmunity, essentially replicating the risk effect of the PTPN22_620W in human autoimmune diseases. Furthermore, findings from mouse models shed new light on both cellular as well as molecular mechanisms of the effect of PTPN22 on adaptive and innate immunity. Here we review recently emerged evidence of the interconnection between mouse PTPN22 and autoimmunity. We also discuss the consistence and discrepancy between findings derived from human and mouse studies.