Abstract
Type 1 diabetes (T1D) is caused by the destruction of β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective treatment for T1D. However, the survival of islet grafts is often disrupted by recurrent autoimmunity. Alpha-lipoic acid (ALA) has been reported to have immunomodulatory effects and, therefore, may have therapeutic potential in the treatment of T1D. In this study, we investigated the therapeutic potential of ALA in autoimmunity inhibition. We treated non-obese diabetic (NOD) mice with spontaneous diabetes and islet-transplantation mice with ALA. The onset of diabetes was decreased and survival of the islet grafts was extended. The populations of Th1 cells decreased, and regulatory T cells (Tregs) increased in ALA-treated mice. The in vitro Treg differentiation was significantly increased by treatment with ALA. The adoptive transfer of ALA-differentiated Tregs into NOD recipients improved the outcome of the islet grafts. Our results showed that in vivo ALA treatment suppressed spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Tregs. Our study also demonstrated the therapeutic potential of ALA in Treg-based cell therapies and islet transplantation used in the treatment of T1D.
Highlights
Autoimmune diabetes, formally referred to as type 1 diabetes (T1D), results from the destruction of insulin-producing β cells in the islets of the pancreas and has been identified as a T cell-mediated autoimmune disease [1]
These results indicated that Alpha-lipoic acid (ALA) treatment had effectively delayed the onset of autoimmune diabetes as well as the infiltration of leukocytes to the islets
Our results demonstrated that ALA treatment had significantly prevented the onset of diabetes and prolonged islet graft survival in non-obese diabetic (NOD) mice
Summary
Autoimmune diabetes, formally referred to as type 1 diabetes (T1D), results from the destruction of insulin-producing β cells in the islets of the pancreas and has been identified as a T cell-mediated autoimmune disease [1]. Chronic T1D leads to many clinical complications including diabetic retinopathy, nephropathy, neuropathy, and macrovascular disease [2].The development of T1D is usually diagnosed in young patients; this disease has been termed “juvenile-onset” or “childhood-onset” diabetes. NOD murine models have frequently been used for T1D studies. These mice have been bred to spontaneously develop T cell-dependent β cell destruction that resembles human T1D especially in the female NOD mice in which develop autoimmune diabetes around 80–90% at 40-weeks-old; female NOD mice often serve as animal models for studies concerning T1D [7]
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