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

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Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice. / Fousteri, Georgia; Jofra, Tatiana; Di Fonte, Roberta; Gagliani, Nicola; Morsiani, Cristina; Stabilini, Angela; Battaglia, Manuela.

In: DIABETOLOGIA, Vol. 58, No. 6, 06.2015, p. 1319-28.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fousteri, G, Jofra, T, Di Fonte, R, Gagliani, N, Morsiani, C, Stabilini, A & Battaglia, M 2015, 'Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice', DIABETOLOGIA, vol. 58, no. 6, pp. 1319-28. https://doi.org/10.1007/s00125-015-3540-9

APA

Fousteri, G., Jofra, T., Di Fonte, R., Gagliani, N., Morsiani, C., Stabilini, A., & Battaglia, M. (2015). Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice. DIABETOLOGIA, 58(6), 1319-28. https://doi.org/10.1007/s00125-015-3540-9

Vancouver

Fousteri G, Jofra T, Di Fonte R, Gagliani N, Morsiani C, Stabilini A et al. Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice. DIABETOLOGIA. 2015 Jun;58(6):1319-28. https://doi.org/10.1007/s00125-015-3540-9

Bibtex

@article{c9b9bf98eb6b412ebf8b27fd82e86e5a,
title = "Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice",
abstract = "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.",
keywords = "Adoptive Transfer, Animals, Autoimmunity, Blood Glucose, Forkhead Transcription Factors, Islets of Langerhans, Islets of Langerhans Transplantation, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Risk Factors, Signal Transduction, T-Lymphocytes, Regulatory, Transplantation Tolerance, Journal Article, Research Support, Non-U.S. Gov't",
author = "Georgia Fousteri and Tatiana Jofra and {Di Fonte}, Roberta and Nicola Gagliani and Cristina Morsiani and Angela Stabilini and Manuela Battaglia",
year = "2015",
month = jun,
doi = "10.1007/s00125-015-3540-9",
language = "English",
volume = "58",
pages = "1319--28",
journal = "DIABETOLOGIA",
issn = "0012-186X",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice

AU - Fousteri, Georgia

AU - Jofra, Tatiana

AU - Di Fonte, Roberta

AU - Gagliani, Nicola

AU - Morsiani, Cristina

AU - Stabilini, Angela

AU - Battaglia, Manuela

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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.

KW - Adoptive Transfer

KW - Animals

KW - Autoimmunity

KW - Blood Glucose

KW - Forkhead Transcription Factors

KW - Islets of Langerhans

KW - Islets of Langerhans Transplantation

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C3H

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 22

KW - Risk Factors

KW - Signal Transduction

KW - T-Lymphocytes, Regulatory

KW - Transplantation Tolerance

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00125-015-3540-9

DO - 10.1007/s00125-015-3540-9

M3 - SCORING: Journal article

C2 - 25748328

VL - 58

SP - 1319

EP - 1328

JO - DIABETOLOGIA

JF - DIABETOLOGIA

SN - 0012-186X

IS - 6

ER -