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T-cell–specific PTPN2 deficiency in NOD mice accelerates the development of type 1 diabetes and autoimmune comorbidities

Wiede, Florian, Brodnicki, Thomas C., Goh, Pei Kee, Leong, Yew A., Jones, Gareth W., Yu, Di, Baxter, Alan G., Jones, Simon A., Kay, Thomas W. H. and Tiganis, Tony 2019. T-cell–specific PTPN2 deficiency in NOD mice accelerates the development of type 1 diabetes and autoimmune comorbidities. Diabetes 68 (6) , pp. 1251-1266. 10.2337/db18-1362

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Publisher: American Diabetes Association
ISSN: 0012-1797
Date of First Compliant Deposit: 15 April 2019
Date of Acceptance: 17 March 2019
Last Modified: 25 Nov 2020 13:05
URI: http://orca.cardiff.ac.uk/id/eprint/121768

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