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Erschienen in:
01.06.2015 | Article
Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice
Erschienen in: Diabetologia | Ausgabe 6/2015
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Aims/hypothesis
Protein tyrosine phosphatase non-receptor 22 (PTPN22) plays a central role in T cell, B cell and innate immune cell signalling. A genetic variation in Ptpn22 is considered a major risk factor for the development of type 1 diabetes and has been the subject of extensive study. While several reports have addressed how Ptpn22 might predispose to autoimmunity, its involvement in other immune-mediated diseases, such as allograft rejection, has not been explored.
Methods
To address a possible function for Ptpn22 in allograft rejection, we used a mouse model of pancreatic islet transplantation. We performed transplant tolerance experiments and determined how PTPN22 shapes tolerance induction and maintenance.
Results
Ptpn22
−/− recipient mice generate higher numbers of alloreactive T cells after allogeneic pancreatic islet transplantation compared with wild-type (WT) mice, but reject grafts with similar kinetics. This is not only due to their well-documented increase in forkhead box protein P3 (FOXP3)+ T regulatory (Treg) cells but also to the expansion of T regulatory type 1 (Tr1) cells caused by the lack of PTPN22. In addition, a tolerogenic treatment known to induce transplant tolerance in WT mice via Tr1 cell generation is more effective in Ptpn22
−/− mice as a consequence of boosting both Tr1 and FOXP3+ Treg cells.
Conclusions/interpretation
A lack of PTPN22 strengthens transplant tolerance to pancreatic islets by expanding both FOXP3+ Treg and Tr1 cells. These data suggest that targeting PTPN22 could serve to boost transplant tolerance.