Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells by their own immune system, resulting in lifelong insulin deficiency. Continuous exogenous insulin replacement therapy is the current standard of care for T1D. Transplantation of primary pancreatic islets or the entire pancreas is a viable remedy for managing patients with autoimmune T1D. However, this strategy is not feasible due to several obstacles, including a scarcity of donors, islet cells, and poor vascular engraftment of islets post-transplantation, as well as the need for prolonged immune suppression. Innovative approaches must be developed to counteract pancreatic β-cell destruction and salvage endogenic insulin production, thereby regulating blood glucose levels. This review includes an overview of autoimmune T1D, immune cells involved in T1D pathophysiology, and immunotherapy-based strategies to treat and prevent autoimmune T1D. Recent immunotherapy progress toward targeting pancreatic islet-specific immune pathways tangled tolerance has fueled the advancement of therapies that may allow for the prevention or reversal of this autoimmune T1D while avoiding other adverse reactions associated with the previous attempt, which was mostly immunosuppressive. As a result, significant efforts are currently underway to improve the efficacy of immunotherapy-based approaches by leveraging the beneficial actions of immune cells, specifically effector CD4+, CD8+, and regulatory T cells. This review will provide an overview of currently available immune-based therapeutic options for T1D and will examine the growing evidence that supports the use of immune cell-based approaches to improve therapeutic outcomes in the prevention or reversal of autoimmune T1D.
Highlights
Autoimmune diseases, which are pathological conditions caused by abnormal immune responses to substances and tissues that are normally present or generated within their own body, affect nearly 23.5 million Americans, with nearly 80 percent of those affected being females
There are over 100 autoimmune diseases known to date, the most common autoimmune disorders are Type 1 Diabetes Mellitus (T1D), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Inflammatory Bowel Disease (IBD), Multiple Sclerosis (MS), GuillainBarre syndrome, chronic inflammatory demyelinating polyneuropathy, Psoriasis, Graves’ disease, and Hashimoto’s disease [1,2]
Targeted and specific immunotherapies must be developed for the treatment of autoimmune T1D to re-establish tolerance mechanisms or eliminate pancreatic cell-specific immune responses generated by primary T and B lymphocytes, which can preserve the destructive β-cell mass for different functions and maintain insulin throughout life
Summary
Autoimmune diseases, which are pathological conditions caused by abnormal immune responses to substances and tissues that are normally present or generated within their own body, affect nearly 23.5 million Americans, with nearly 80 percent of those affected being females. The heterogeneity associated with human autoimmune T1D, as well as the nature of islet inflammation, reflects the individual’s genotype and type of environmental insult These factors influence which immune effectors are important in the pathophysiology of autoimmune T1D, the rate of disease progression, and the degree of pancreatic islet-specific β-cell dysregulation and/or death [8,9,10,11]. Targeted and specific immunotherapies must be developed for the treatment of autoimmune T1D to re-establish tolerance mechanisms or eliminate pancreatic cell-specific immune responses generated by primary T and B lymphocytes, which can preserve the destructive β-cell mass for different functions and maintain insulin throughout life. This review discusses the general history of T1D, immune cells involved in the pathophysiology of autoimmune Type 1 diabetes, and immunotherapy‐based treatment strategies for T1D
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