ReviewRoles of the protein tyrosine phosphatase PTPN22 in immunity and autoimmunity

- PTPN22 predisposes to autoimmunity and is considered a prominent therapeutic target.
- PTPN22 is involved in TCR, BCR and innate immune (i.e. TLR) signaling pathways.
- Murine studies show that the PTPN22*W variant renders T and B cells hyper responsive.
- Controversy in human data: gain and loss-of-function role for PTPN22*W is reported.

PTPN22 is a protein tyrosine phosphatase expressed by the majority of cells belonging to the innate and adaptive immune systems. Polymorphisms in PTPN22 are associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type 1 diabetes. This review discusses the role of PTPN22 in T and B cells, and its function in innate immune cells, such as monocytes, dendritic cells and NK cells. We focus particularly on the complexity that underlies the function of PTPN22 in the biological processes of the immune system; such complexity has led various research groups to produce rather conflicting data.