التفاصيل البيبلوغرافية
| العنوان: |
TYK2, a Candidate Gene for Type 1 Diabetes, Modulates Apoptosis and the Innate Immune Response in Human Pancreatic β-Cells. |
| المؤلفون: |
Marroqui, Laura, Sousa Dos Santos, Reinaldo, Fløyel, Tina, Grieco, Fabio A., Santin, Izortze, Op de beeck, Anne, Marselli, Lorella, Marchetti, Piero, Pociot, Flemming, Eizirik, Decio L., Dos Santos, Reinaldo Sousa |
| المصدر: |
Diabetes; Nov2015, Vol. 64 Issue 11, p3808-3817, 10p, 1 Diagram, 6 Graphs |
| مصطلحات موضوعية: |
TYPE 1 diabetes, GENES, APOPTOSIS, IMMUNE response, PANCREATIC beta cells, INTERFERONS, INFLAMMATION, MAJOR histocompatibility complex, PROTEIN metabolism, CELL lines, CELL physiology, CYTOKINES, GENETIC polymorphisms, IMMUNITY, ISLANDS of Langerhans, PHOSPHORYLATION, PROTEINS, TRANSFERASES, SEQUENCE analysis |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder