| First Author | Wiede F | Year | 2019 |
| Journal | Diabetes | Volume | 68 |
| Issue | 6 | Pages | 1251-1266 |
| PubMed ID | 30936146 | Mgi Jnum | J:276219 |
| Mgi Id | MGI:6306217 | Doi | 10.2337/db18-1362 |
| Citation | Wiede F, et al. (2019) T-Cell-Specific PTPN2 Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Comorbidities. Diabetes 68(6):1251-1266 |
| abstractText | 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 Sjogren syndrome. Although PTPN2 deficiency in CD8(+) T cells alone was able to drive the destruction of pancreatic beta-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. |
