Chapters authored
The Innate Immune System via Toll-Like Receptors (TLRs) in Type 1 Diabetes - Mechanistic Insights
Type 1 diabetes (T1D) is a form of diabetes mellitus resulting from the lack of insulin secretion by the pancreatic beta cells and which accounts for approximately 5% of the total number of patients with diabetes worldwide. T1D is one of the most common endocrine disorders of children, and its incidence is steadily increasing. T1D is largely considered an autoimmune disorder resulting from the specific destruction of the pancreatic beta-cells that produce insulin. However, T1D pathophysiology is still not completely understood, and although insulin and other therapies ameliorate the manifestations of the disease, no cure is currently available. Traditionally, T1D has been thought of as a condition of cellular adaptive immunity, but evidence exists that components of the innate immune system, such as Toll-like receptors (TLRs), play a critical role in T1D development. TLRs have a central role in sensing microbial infections as well as endogenous alarm signals and trigger the release of inflammatory cytokines. The involvement of these receptors in the pathophysiology of several chronic diseases has become a major research interest, and in the last two decades, many studies have suggested the involvement of the innate immune system in the mechanism triggering T1D. Furthermore, microvascular complications in diabetic patients result in considerable morbidity, particularly diabetic nephropathy, retinopathy, and atherosclerosis. A hallmark of diabetic vascular pathology is inflammation and endothelial dysfunction. Recent literature suggests that TLR signaling is involved in vascular inflammation and endothelial dysfunction and that TLR activation may play a crucial role in diabetic microangiopathy. However, the mechanisms by which TLRs and their ligands contribute to T1D are not yet clear, and further investigation is needed. The goal of the present chapter is to address the contribution of TLRs to the mechanisms leading to the development and progression of T1D and to review current possibilities of targeting TLRs to forestall diabetic complications.
Part of the book: Major Topics in Type 1 Diabetes