| First Author | Anguela XM | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 2 | Pages | 551-60 |
| PubMed ID | 23099863 | Mgi Jnum | J:208607 |
| Mgi Id | MGI:5563757 | Doi | 10.2337/db11-1776 |
| Citation | Anguela XM, et al. (2013) Nonviral-mediated hepatic expression of IGF-I increases Treg levels and suppresses autoimmune diabetes in mice. Diabetes 62(2):551-60 |
| abstractText | In type 1 diabetes, loss of tolerance to beta-cell antigens results in T-cell-dependent autoimmune destruction of beta cells. The abrogation of autoreactive T-cell responses is a prerequisite to achieve long-lasting correction of the disease. The liver has unique immunomodulatory properties and hepatic gene transfer results in tolerance induction and suppression of autoimmune diseases, in part by regulatory T-cell (Treg) activation. Hence, the liver could be manipulated to treat or prevent diabetes onset through expression of key genes. IGF-I may be an immunomodulatory candidate because it prevents autoimmune diabetes when expressed in beta cells or subcutaneously injected. Here, we demonstrate that transient, plasmid-derived IGF-I expression in mouse liver suppressed autoimmune diabetes progression. Suppression was associated with decreased islet inflammation and beta-cell apoptosis, increased beta-cell replication, and normalized beta-cell mass. Permanent protection depended on exogenous IGF-I expression in liver nonparenchymal cells and was associated with increased percentage of intrapancreatic Tregs. Importantly, Treg depletion completely abolished IGF-I-mediated protection confirming the therapeutic potential of these cells in autoimmune diabetes. This study demonstrates that a nonviral gene therapy combining the immunological properties of the liver and IGF-I could be beneficial in the treatment of the disease. |
