| First Author | Rondas D | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 2 | Pages | 573-86 |
| PubMed ID | 25204978 | Mgi Jnum | J:246941 |
| Mgi Id | MGI:5924561 | Doi | 10.2337/db14-0621 |
| Citation | Rondas D, et al. (2015) Citrullinated glucose-regulated protein 78 is an autoantigen in type 1 diabetes. Diabetes 64(2):573-86 |
| abstractText | Posttranslational modifications of self-proteins play a substantial role in the initiation or propagation of the autoimmune attack in several autoimmune diseases, but their contribution to type 1 diabetes is only recently emerging. In the current study, we demonstrate that inflammatory stress, induced by the cytokines interleukin-1beta and interferon-gamma, leads to citrullination of GRP78 in beta-cells. This is coupled with translocation of this endoplasmic reticulum chaperone to the beta-cell plasma membrane and subsequent secretion. Importantly, expression and activity of peptidylarginine deiminase 2, one of the five enzymes responsible for citrullination and a candidate gene for type 1 diabetes in mice, is increased in islets from diabetes-prone nonobese diabetic (NOD) mice. Finally, (pre)diabetic NOD mice have autoantibodies and effector T cells that react against citrullinated GRP78, indicating that inflammation-induced citrullination of GRP78 in beta-cells generates a novel autoantigen in type 1 diabetes, opening new avenues for biomarker development and therapeutic intervention. |
