Type 1 diabetes (T1D) is a chronic autoimmune disease in which the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas, leading to lifelong insulin dependence. Managing T1D remains challenging, as most patients struggle to maintain optimal glucose levels, increasing their risk of acute and chronic complications. Research suggests that environmental factors, such as vitamin D deficiency, may contribute to T1D development, prompting investigations into vitamin D supplementation as a preventive strategy. In this PhD project, high-dose vitamin D (800 IU) was shown to prevent T1D in mice by promoting regulatory immune responses, though this dosage may pose safety concerns for humans. Additionally, vitamin D influenced the gut microbiome, though its precise role in disease prevention remains unclear. Another promising approach explored in this work is antigen-specific immunotherapy, where insulin peptide vaccination formulated with alum effectively induced regulatory T cells in mice, helping to prevent T1D. Given the increasing recognition that T1D is a heterogeneous disease, disease endotyping has emerged as a crucial strategy for developing personalized treatments based on genetic and immune profiles. In the final part of this research, a combination therapy using anti-mouse thymocyte globulin (mATG) and verapamil demonstrated long-term remission in mice by restoring immune balance and supporting beta cell survival. Ongoing clinical trials within the INNODIA framework aim to refine these therapeutic approaches and accelerate their translation into human treatments. As T1D research advances, these innovative strategies offer hope that one day a cure will eliminate the need for insulin therapy.
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