T Cell-Specific PTPN2-Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Co-Morbidities.

Florian Wiede*, Thomas C. Brodnicki, Pei Kee Goh, Yew A. Leong, Gareth W. Jones, Di Yu, Alan G. Baxter, Simon A. Jones, Thomas W.H. Kay, Tony Tiganis

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

2 Citations (Scopus)
182 Downloads (Pure)

Abstract

Genome-wide association studies have identified PTPN2 as an important non-MHC gene for autoimmunity. Single nucleotide polymorphisms that reduce PTPN2 expression have been linked with the development of various autoimmune disorders, including type 1 diabetes. The tyrosine phosphatase PTPN2 attenuates T-cell receptor and cytokine signaling in T cells to maintain peripheral tolerance, but the extent to which PTPN2 deficiency in T cells might influence type 1 diabetes onset remains unclear. NOD mice develop spontaneous autoimmune type 1 diabetes similar to that seen in humans. In this study, T-cell PTPN2 deficiency in NOD mice markedly accelerated the onset and increased the incidence of type 1 diabetes as well as that of other disorders, including colitis and Sjögren syndrome. Although PTPN2 deficiency in CD8 + T cells alone was able to drive the destruction of pancreatic β-cells and the onset of diabetes, T-cell-specific PTPN2 deficiency was also accompanied by increased CD4 + T-helper type 1 differentiation and T-follicular-helper cell polarization and increased the abundance of B cells in pancreatic islets as seen in human type 1 diabetes. These findings causally link PTPN2 deficiency in T cells with the development of type 1 diabetes and associated autoimmune comorbidities.

Original languageEnglish
Pages (from-to)1251-1266
Number of pages16
JournalDiabetes
Volume68
Issue number6
Early online date20 May 2019
DOIs
Publication statusPublished - 1 Jun 2019

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    Wiede, F., Brodnicki, T. C., Goh, P. K., Leong, Y. A., Jones, G. W., Yu, D., Baxter, A. G., Jones, S. A., Kay, T. W. H., & Tiganis, T. (2019). T Cell-Specific PTPN2-Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Co-Morbidities. Diabetes, 68(6), 1251-1266. https://doi.org/10.2337/db18-1362