| First Author | Liadis N | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 9 | Pages | 3620-9 |
| PubMed ID | 15831467 | Mgi Jnum | J:97650 |
| Mgi Id | MGI:3575980 | Doi | 10.1128/MCB.25.9.3620-3629.2005 |
| Citation | Liadis N, et al. (2005) Caspase-3-Dependent {beta}-Cell Apoptosis in the Initiation of Autoimmune Diabetes Mellitus. Mol Cell Biol 25(9):3620-9 |
| abstractText | beta-Cell apoptosis is a key event contributing to the pathogenesis of type 1 diabetes mellitus. In addition to apoptosis being the main mechanism by which beta cells are destroyed, beta-cell apoptosis has been implicated in the initiation of type 1 diabetes mellitus through antigen cross-presentation mechanisms that lead to beta-cell-specific T-cell activation. Caspase-3 is the major effector caspase involved in apoptotic pathways. Despite evidence supporting the importance of beta-cell apoptosis in the pathogenesis of type 1 diabetes, the specific role of caspase-3 in this process is unknown. Here, we show that Caspase-3 knockout (Casp3(-)(/-)) mice were protected from developing diabetes in a multiple-low-dose streptozotocin autoimmune diabetes model. Lymphocyte infiltration of the pancreatic islets was completely absent in Casp3(-)(/-) mice. To determine the role of caspase-3-dependent apoptosis in disease initiation, a defined antigen-T-cell receptor transgenic system, RIP-GP/P14 double-transgenic mice with Casp3 null mutation, was examined. beta-cell antigen-specific T-cell activation and proliferation were observed only in the pancreatic draining lymph node of RIP-GP/P14/Casp3(+)(/-) mice, but not in mice lacking caspase-3. Together, our findings demonstrate that caspase-3-mediated beta-cell apoptosis is a requisite step for T-cell priming, a key initiating event in type 1 diabetes. |
