دورية أكاديمية
TYK2 , a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic β-Cells
| العنوان: | TYK2 , a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic β-Cells |
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| المؤلفون: | Marroqui, Laura, Dos Santos, Reinaldo Sousa, Fløyel, Tina, Grieco, Fabio A, Santin, Izortze, Op de Beeck, Anne, Marselli, Lorella, Marchetti, Piero, Pociot, Flemming, Eizirik, Decio L |
| المصدر: | Marroqui , L , Dos Santos , R S , Fløyel , T , Grieco , F A , Santin , I , Op de Beeck , A , Marselli , L , Marchetti , P , Pociot , F & Eizirik , D L 2015 , ' TYK2 , a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic β-Cells ' , Diabetes , vol. 64 , no. 11 , pp. 3808-17 . https://doi.org/10.2337/db15-0362Test |
| سنة النشر: | 2015 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | Apoptosis, Cell Line, Cell Survival, Chemokine CXCL10, Diabetes Mellitus, Type 1, Genes, MHC Class I, Genome-Wide Association Study, Humans, Immunity, Innate, Insulin-Secreting Cells, Interferon-alpha, Phosphorylation, Polymorphism, Single Nucleotide, TYK2 Kinase |
| الوصف: | Pancreatic β-cells are destroyed by an autoimmune attack in type 1 diabetes. Linkage and genome-wide association studies point to >50 loci that are associated with the disease in the human genome. Pathway analysis of candidate genes expressed in human islets identified a central role for interferon (IFN)-regulated pathways and tyrosine kinase 2 (TYK2). Polymorphisms in the TYK2 gene predicted to decrease function are associated with a decreased risk of developing type 1 diabetes. We presently evaluated whether TYK2 plays a role in human pancreatic β-cell apoptosis and production of proinflammatory mediators. TYK2-silenced human β-cells exposed to polyinosinic-polycitidilic acid (PIC) (a mimick of double-stranded RNA produced during viral infection) showed less type I IFN pathway activation and lower production of IFNα and CXCL10. These cells also had decreased expression of major histocompatibility complex (MHC) class I proteins, a hallmark of early β-cell inflammation in type 1 diabetes. Importantly, TYK2 inhibition prevented PIC-induced β-cell apoptosis via the mitochondrial pathway of cell death. The present findings suggest that TYK2 regulates apoptotic and proinflammatory pathways in pancreatic β-cells via modulation of IFNα signaling, subsequent increase in MHC class I protein, and modulation of chemokines such as CXCL10 that are important for recruitment of T cells to the islets. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.2337/db15-0362 |
| الإتاحة: | https://doi.org/10.2337/db15-0362Test https://curis.ku.dk/portal/da/publications/tyk2-a-candidate-gene-for-type-1-diabetes-modulates-apoptosis-and-the-innate-immune-response-in-human-pancreatic-cellsTest(7491d0b8-89f9-42a6-8a76-ad509e04f9e2).html |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.11992C6A |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db15-0362 |
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