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T cell-specific PTPN2-deficiency in NOD mice accelerates the development of type 1 diabetes and autoimmune co-morbidities.

Wiede, Florian, Brodnicki, Tom, Goh, Pei Kee, Leong, Yew A., Jones, Gareth, Yu, Di, Baxter, Alan G., Jones, Simon, Kay, Tom and Tiganis, Tony 2019. T cell-specific PTPN2-deficiency in NOD mice accelerates the development of type 1 diabetes and autoimmune co-morbidities. 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: 27 Jun 2019 14:46
URI: http://orca.cf.ac.uk/id/eprint/121768

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