First Author | Xia F | Year | 2016 |
Journal | J Leukoc Biol | Volume | 99 |
Issue | 6 | Pages | 1131-40 |
PubMed ID | 26667474 | Mgi Jnum | J:243091 |
Mgi Id | MGI:5907583 | Doi | 10.1189/jlb.3A0815-371RRR |
Citation | Xia F, et al. (2016) Reg3g overexpression promotes beta cell regeneration and induces immune tolerance in nonobese-diabetic mouse model. J Leukoc Biol 99(6):1131-40 |
abstractText | The regenerating islet-derived gene was first isolated in regenerated pancreas tissues, greatly contributing to beta cell regeneration. It is an anti-inflammatory in response to cellular stress. This encouraged us to investigate the exact role of a novel member of Reg family, regenerating islet-derived gene gamma, in type 1 diabetes of nonobese-diabetic mice. For this, Reg3g gene was overexpressed in pancreatic islets, and conferred beneficial effects on beta cell regeneration through activating the Janus kinase 2/signal transducer and activator of transcription 3/nuclear factor kappaB signaling pathway. Lentiviral vector-encoding regenerating islet-derived gene gamma treatment also decreased lymphocyte infiltrates of the intra-islet and peri-islet by inducing both differentiation of regulatory T cell and immature dendritic cells of tolerogenic properties, which attenuated autoimmunity. This treatment further contributed to rebalanced levels of type 1/2 helper T cell cytokines and elevated alpha1-antitrypsin levels in the serum. These results were not observed in phosphate-buffered saline-treated mice or in lentivirus-control mice. We have shown, for the first time, to our knowledge, that regenerating islet-derived gene gamma promotes beta cell regeneration and preserves beta cells from autoimmunity damage by increasing regulatory T cell differentiation and inducing tolerated dendritic cells. This regenerating islet-derived gene gamma infusion could probably be developed into an optimal gene therapy for the prevention and reversal of type 1 diabetes. |