Altered Immune Regulation in Type 1 Diabetes

Abstract

Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

“…The development of T1D is generally presumed to be a result of interactions between the immune system and an intricate network of genetic and environmental factors (Zoka et al, 2013). An important role of innate inflammation has been established in the insulitic process of T1D, in the form of a 'dialog' between invading immune cells and target β cells (Eizirik et al, 2009).…”

Low Levels of Vitamin D correlate with Hemoglobin A1c and Interleukin-10 Levels in Pediatric Type 1 Diabetes Mellitus Patients

“…Type 1 diabetes results from autoimmune destruction of insulin-producing β cells in the islets of the pancreas [1]. Failure mechanisms of immunoregulator cause autoreactive T cells, inflammatory process in the islets and damage the pancreatic β cell [2,3]. Vitamin D deficiency may increase the risk of developing autoimmune diseases including type 1 diabetes mellitus.…”

Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies

“…Diabetes-related autoantibodies are secondary factors for the development of the disease [ 165 ]. Molecules from HLA (Human Leukocyte Antigen) class I and class II are involved in the T cell repertoire selection during maturation of the immune system in the thymus, as well as activation and regulation of the adaptive immune response [ 166 ].…”