T-Cell–Specific PTPN2 Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Comorbidities
| Autor: | Thomas W.H. Kay, Yew Ann Leong, Tony Tiganis, Pei Kee Goh, Di Yu, Thomas C. Brodnicki, Florian Wiede, Simon Arnett Jones, Gareth W. Jones, Alan G. Baxter |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine T-Lymphocytes Endocrinology Diabetes and Metabolism T cell 030209 endocrinology & metabolism CD8-Positive T-Lymphocytes medicine.disease_cause Major histocompatibility complex Autoimmune Diseases Autoimmunity Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine Mice Inbred NOD Internal Medicine medicine Animals NOD mice Protein Tyrosine Phosphatase Non-Receptor Type 2 Type 1 diabetes biology business.industry Pancreatic islets Peripheral tolerance Th1 Cells Colitis medicine.disease Diabetes Mellitus Type 1 Sjogren's Syndrome 030104 developmental biology medicine.anatomical_structure Immunology biology.protein business CD8 |
| Zdroj: | 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, vol. 68, no. 6, pp. 1251-1266 . https://doi.org/10.2337/db18-1362 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db18-1362 |
| Popis: | Genome-wide association studies have identified PTPN2 as an important non-major histocompatibility complex gene for autoimmunity. Single nucleotide polymorphisms that reduce PTPN2 expression have been linked with the development of varied autoimmune disorders, including type 1 diabetes. The tyrosine-phosphatase PTPN2 attenuates T cell receptor and cytokine signalling 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. Non-Obese Diabetic (NOD) mice develop spontaneous autoimmune type 1 diabetes, similar to that seen in humans. 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’s syndrome. Although PTPN2-deficiency in CD8+ T cells alone was able to drive the destruction of pancreatic β cells and onset of diabetes, T cell-specific PTPN2-deficiency was also accompanied by increased CD4+ T-helper type 1 differentiation and T follicular helper cell polarisation and an increased 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 co-morbidities. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|