Examining immunotherapeutics in type 1 diabetes mellitus
OA Version
Citation
Abstract
Type I diabetes mellitus (T1DM) is an autoimmune disease that develops due to a loss of immunological tolerance. This loss of immunological tolerance permits the escape of autoreactive lymphocytes that target and destroy the β cells of the pancreas. As a result, patients lose their ability to make and secrete insulin known as insulinopenia. Subsequently, a loss of insulin disrupts blood glucose regulation and ultimately leads to hyperglycemia. Hyperglycemia is a serious condition that can and will lead to death if not addressed. The immune system is made up of dozens of signaling, adhesion, and surface molecules that aid immune function. Immunity is divided into two groups: innate immunity and adaptive immunity. Both divisions contribute to the effectiveness of the system, protecting the body from infections. Innate immunity serves as the first responder, working together with the adaptive immune system. This feedback loop sustains immune activity. Though powerful, immune responses can easily damage tissue if not regulated. Thus, there are regulatory macrophages, dendritic cells, and lymphocytes that control immunity and maintain central and peripheral tolerance. Immune cells must be able to distinguish foreign bodies from the host’s tissues. This tolerance is important for preventing immune cells from reacting and destroying host tissues. As seen in autoimmune diseases such as T1DM, any disruption in this ability can lead to devastating impacts on tissue systems. The development of immunotherapies has provided new strategies to counteract autoimmunity by leveraging components of the immune systems. Various treatments, including pancreas islet transplants, as well as insulin therapy, are commonly used and are typically paired with immunosuppressive drugs. One such immunosuppressor, teplizumab, is the first FDA-approved treatment shown to delay the onset of T1DM. However, long-term immunosuppression carries the risk of cytotoxic effects. Current treatments primarily focus on managing T1DM rather than preventing its onset. To address this, T regulatory cells (Tregs) have been used to generate regulatory cells that target certain cell populations. Research has demonstrated that polyclonal, engineered T cell receptors (TCR), and chimeric antigen receptor (CAR) Tregs can halt T1DM progression in animal models. Unfortunately, findings in animal studies do not always translate to human applications, highlighting the need for further refinement of such studies. Currently, combination therapy remains the most reliable treatment option for patients, however, continued emphasis on Tregs and immune tolerance restoration will be essential for advancing T1DM prevention strategies.
Description
2025