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- Title
T-Cell–Specific PTPN2 Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Comorbidities.
- Authors
Wiede, Florian; Brodnicki, Thomas C.; Pei Kee Goh; Leong, Yew A.; Jones, Gareth W.; Di Yu; Baxter, Alan G.; Jones, Simon A.; Kay, Thomas W. H.; Tiganis, Tony
- 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.
- Subjects
TYPE 1 diabetes; PANCREATIC beta cells; PROTEIN-tyrosine phosphatase; SINGLE nucleotide polymorphisms; T cells
- Publication
Diabetes, 2019, Vol 68, Issue 6, p1251
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db18-1362