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Publication : Reg3g overexpression promotes β cell regeneration and induces immune tolerance in nonobese-diabetic mouse model.

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.
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