Abstract
Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS) by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation.
Highlights
Type 1 diabetes (T1D) is an autoimmune disease characterized by chronic inflammation where self-reactive immune responses selectively target and destroy β-cells within the pancreas
In a majority of patients, insulin therapies can help regulate the rapid variations in blood glucose levels that result from this autoimmune attack, this is not a cure and for a relatively large number of patients, exogenous insulin treatment is not enough for them to maintain stable blood glucose levels [1]
To understand why these aberrant signaling pathways and the corresponding redox responses are vital at various stages of islet transplantation, it is necessary to acknowledge the interplay between redox signaling and inflammatory responses
Summary
Type 1 diabetes (T1D) is an autoimmune disease characterized by chronic inflammation where self-reactive immune responses selectively target and destroy β-cells within the pancreas. The persistent challenges in early detection and the minimal effectiveness of immunotherapies have lead to a search for alternative treatment options to restore the functionality of insulin regulation in individuals after the destruction of β-cells has already occurred One such attractive therapy is islet transplantation. The presence of oxidative species such as hydrogen peroxide (H2O2) and superoxide anions (O2− ) can impact glucose sensing within the β-cell [29], but they can serve as a third signal to promote the maturation and expansion of β-cell-specific autoreactive T cell subsets [30,31,32] These autoreactive immune responses can initiate the destruction of β-cells though either the induction of apoptosis using the FAS pathway or by necrosis through the release of pro-inflammatory cytokines, perforin, granzyme B, and ROS [33, 34]. The hope is that attenuating the redox status of the islets themselves or the surrounding microenvironment will promote islet function and prolong graft viability without the need for toxic immunosuppressive drugs
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