دورية أكاديمية
Primary human and rat β-Cells release the intracellular autoantigens GAD65, IA-2, and proinsulin in exosomes together with cytokine-induced enhancers of immunity
| العنوان: | Primary human and rat β-Cells release the intracellular autoantigens GAD65, IA-2, and proinsulin in exosomes together with cytokine-induced enhancers of immunity |
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| المؤلفون: | Cianciaruso, C., Phelps, E. A., Pasquier, M., Hamelin, R., Demurtas, D., Ahmed, M. A., Hirosue, S., Swartz, M. A., De Palma, M., Hubbell, J. A., Baekkeskov, S., PIEMONTI, LORENZO |
| المساهمون: | Cianciaruso, C., Phelps, E. A., Pasquier, M., Hamelin, R., Demurtas, D., Ahmed, M. A., Piemonti, Lorenzo, Hirosue, S., Swartz, M. A., De Palma, M., Hubbell, J. A., Baekkeskov, S. |
| بيانات النشر: | American Diabetes Association Inc. |
| سنة النشر: | 2017 |
| الوصف: | The target autoantigens in several organ-specific autoimmune diseases, including type 1 diabetes (T1D), are intracellularmembrane proteins, whose initial encounter with the immune system is poorly understood. Here we propose a new model for how these proteins can initiate autoimmunity. We found that rat and human pancreatic islets release the intracellular β-cell autoantigens in human T1D, GAD65, IA-2, and proinsulin in exosomes, which are taken up by and activate dendritic cells. Accordingly, the anchoring of GAD65 to exosome-mimetic liposomes strongly boosted antigen presentation and T-cell activation in the context of the human T1D susceptibility haplotype HLADR4. Cytokine-induced endoplasmic reticulum stress enhanced exosome secretion by β-cells; induced exosomal release of the immunostimulatory chaperones calreticulin, Gp96, and ORP150; and increased exosomal stimulation of antigen-presenting cells. We propose that stress-induced exosomal release of intracellular autoantigens and immunostimulatory chaperonesmay play a role in the initiation of autoimmune responses in T1D. © 2017 by the American Diabetes Association. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/WOS:000392691000023; volume:66; issue:2; firstpage:460; lastpage:473; numberofpages:14; journal:DIABETES; http://hdl.handle.net/20.500.11768/61149Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85011660552; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85011660552&doi=10.2337%2fdb16-0671&partnerID=40&md5=b34cad165f10366c3ec33f550718b7c6Test |
| DOI: | 10.2337/db16-0671 |
| الإتاحة: | https://doi.org/20.500.11768/61149Test https://doi.org/10.2337/db16-0671Test https://hdl.handle.net/20.500.11768/61149Test |
| رقم الانضمام: | edsbas.DDB825D4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db16-0671 |
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