Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice

Diabetologia
Georgia FousteriManuela Battaglia

Abstract

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. 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. 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 Ptp...Continue Reading

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Citations

Jun 9, 2015·Cellular & Molecular Immunology·Hanyu ZengLihua Chen
Jul 29, 2017·World Journal of Diabetes·Giuseppe Galvani, Georgia Fousteri
Mar 5, 2018·Bio-protocol·Tatiana JofraManuela Battaglia
Jul 25, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel J PerryTodd M Brusko
Mar 5, 2018··Giuseppe GalvaniGregori Silvia

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