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

Autor: Cristina Morsiani, Tatiana Jofra, Manuela Battaglia, Roberta Di Fonte, Georgia Fousteri, Nicola Gagliani, Angela Stabilini
Přispěvatelé: Fousteri, Georgia, Jofra, Tatiana, Di Fonte, Roberta, Gagliani, Nicola, Morsiani, Cristina, Stabilini, Angela, Battaglia, Manuela
Rok vydání: 2015
Předmět:
Blood Glucose
endocrine system diseases
Endocrinology
Diabetes and Metabolism
Islets of Langerhans Transplantation
Autoimmunity
Protein tyrosine phosphatase
medicine.disease_cause
T-Lymphocytes
Regulatory
Mice
Risk Factors
immune system diseases
skin and connective tissue diseases
Mice
Knockout
Mice
Inbred BALB C
Mice
Inbred C3H
FOXP3
Forkhead Transcription Factors
PTPN22
Adoptive Transfer
Tr1 cell
medicine.anatomical_structure
Transplantation Tolerance
Pancreatic islet transplantation
Signal Transduction
musculoskeletal diseases
T cell
Mice
Transgenic
G-CSF
Biology
Islets of Langerhans
Transplant tolerance
Internal Medicine
medicine
Animals
Rapamycin
Alloreactivity
B cell
Animal
Risk Factor
Pancreatic islets
Islets of Langerhan
Protein Tyrosine Phosphatase
Non-Receptor Type 22
Forkhead Transcription Factor
Treg cell
eye diseases
Mice
Inbred C57BL
Immunology
Zdroj: Diabetologia. 58:1319-1328
ISSN: 1432-0428
0012-186X
DOI: 10.1007/s00125-015-3540-9
Popis: 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.
Databáze: OpenAIRE
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