Robert Leonard

Introduction: Type I diabetes (T1D) is a chronic autoimmune disease where self-reactive T cells damage insulin-producing pancreatic beta cells resulting in hyperglycemia¹. The etiology is unclear but evidence suggests it arises from an environmental trigger with genetic predisposition¹. Treatment of T1D, although advancing, still consists of insulin replacement therapy in the face of increasing prevalence worldwide^1,2. Immunosuppressive regulatory T cells (Tregs) have been shown to inhibit self-reactive T cells, but are defective in several autoimmune diseases, including T1D³. Thus, harnessing Tregs to suppress autoimmunity has emerged as a potential therapeutic. Methods: An in-vitro method utilized blood samples of 85 diabetic human volunteers. Cell proliferation assays were used to measure the efficacy of Tregs and HbA1c. An in-vivo method administered five days of low dose IL-2 in non-obese diabetic (NOD) mice at the start of diabetic onset. Transcriptome analysis showed levels of gene expression in the Treg cells and glucose testing measured presence of T1D. Insulin mimetypes with increased stimulatory capacities for insulin-reactive T cells were used in mice with human immune systems. Results: In-vitro, researchers suggest that higher levels of active Tregs correlate with improved A1C control when administering IL-2, a Treg stimulator⁴. Using an in-vivo model in mice, IL-2 administration induced diabetes remission in 60% of mice within one week with most remaining normoglycemic over ten weeks after the experiment. Five mice were selected for follow-up after 50 weeks and were still diabetes-free⁵. Administration of IL-2 increased levels of Tregs and decreased levels of interferon gamma in the pancreases of pre-diabetic mice⁶. Lastly, scientists found that using insulin mimetypes promotes enhanced levels of insulin-specific Treg induction in humanized mice⁶.Conclusions: Research suggests that Tregs have an important immunosuppressive function and are damaged in T1D. Mobilizing Tregs in T1D models has shown to decrease pancreatic damage, increase insulin production, and reverse diabetes. Together, it provides an alternative to insulin replacement treatment by stopping the progression of T1D at its onset instead of dealing with the aftermath for the rest of life.

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