Prevention of autoimmune diabetes and islet allograft rejection by beta cell expression of XIAP: Insight into possible mechanisms of local immunomodulation
作者： Mercè Obach , Azadeh Hosseini-Tabatabaei , Joel Montane , Katarina Wind , Galina Soukhatcheva
DOI: 10.1016/J.MCE.2018.05.015
关键词: Beta cell 、 XIAP 、 Streptozotocin 、 Inhibitor of apoptosis 、 Islet 、 Monocarboxylate transporter 1 、 Medicine 、 Lactate dehydrogenase 、 Insulitis 、 Cancer research
摘要: Overexpression of the X-linked inhibitor apoptosis (XIAP) prevents islet allograft rejection. We constructed an adeno-associated virus expressing XIAP driven by rat insulin promoter (dsAAV8-RIP-XIAP) for long-term beta-cell gene expression in vivo. Pancreatic delivery dsAAV8-RIP-XIAP prevented autoimmune diabetes 70% non-obese diabetic (NOD) mice, associated with decreased insulitis. Islets from Balb/c mice transduced were protected following transplantation into streptozotocin (STZ)-diabetic Bl/6 recipients, graft infiltration. Interestingly, transduction induced lactate dehydrogenase (LDHA) and monocarboxylate transporter 1 (MCT1), two genes normally suppressed beta cells involved production release lactate, a metabolite known to suppress local immune responses. Transduction islets AAV8-RIP-LDHA-MCT1 tended prolong survival transplant STZ-diabetic recipients. These findings suggest that has therapeutic potential raise possibility may play role XIAP-mediated immunomodulation.
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