| First Author | Fousteri G | Year | 2015 |
| Journal | Diabetologia | Volume | 58 |
| Issue | 6 | Pages | 1319-28 |
| PubMed ID | 25748328 | Mgi Jnum | J:220848 |
| Mgi Id | MGI:5636556 | Doi | 10.1007/s00125-015-3540-9 |
| Citation | Fousteri G, et al. (2015) Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice. Diabetologia 58(6):1319-28 |
| abstractText | 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. |
