New Insight Into Early Events in Type 1 Diabetes: Role for Islet Stem Cell Exosomes

  1. Ana Lukic1
  1. 1Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Kragujevac, Serbia
  2. 2Institute of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
  1. Corresponding author: Miodrag L. Lukic, miodrag.lukic{at}medf.kg.ac.rs.

Type 1 diabetes (T1D) is an autoimmune disease in which an inappropriate self-directed immune response affects and destroys insulin-producing β-cells in pancreatic islets leading to dysregulated blood glucose levels. T1D may affect people of any age, its clinical presentation is highly variable, and its incidence is increasing worldwide (1). The initial triggering events of T1D are unknown and their elucidation is of pivotal importance. Several factors might lead to the breakdown of β-cell–specific T-cell tolerance, including genetics, exogenous infectious pathogen, noninfectious environment agents, endogenous superantigens, or physiological stress events (2).

The hallmark of autoimmune diabetes is insulitis, which progresses to a destruction of β-cells that results in clinical T1D. An altered balance between proinflammatory T-helper type 1 (Th1)/Th17 cells (γ-interferon [IFN-γ], interleukin [IL]-17) and Th2 immune response (IL-4, IL-10) leads to T1D (3,4). Evidence also suggests that both genetic and environmental factors may induce local inflammatory response, where activated intraislet dendritic cells (DCs) prevent peripheral T-cell tolerance (5). Moreover, it has been recently demonstrated that the development of destructive insulitis is partly due to impaired islet-resident Foxp3+ regulatory T cells (6,7).

Several animal experimental models have been used for the investigation of the pathogenesis of T1D and it appears that a NOD mouse is the model of choice. NOD mice spontaneously develop early peri-insulitis and later intraislet insulitis caused by autoreactive T cells, …

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  1. doi: 10.2337/db13-1786 Diabetes vol. 63 no. 3 835-837
  1. Free via Open Access: OA