Neutrophils in type 1 diabetes

Abstract

Type 1 diabetes is an autoimmune disease that afflicts millions of people worldwide. It occurs as the consequence of destruction of insulin‐producing pancreatic β‐cells triggered by genetic and environmental factors. The initiation and progression of the disease involves a complicated interaction between β‐cells and immune cells of both innate and adaptive systems. Immune cells, such as T cells, macrophages and dendritic cells, have been well documented to play crucial roles in type 1 diabetes pathogenesis. However, the particular actions of neutrophils, which are the most plentiful immune cell type and the first immune cells responding to inflammation, in the etiology of this disease might indeed be unfairly ignored. Progress over the past decades shows that neutrophils might have essential effects on the onset and perpetuation of type 1 diabetes. Neutrophil‐derived cytotoxic substances, including degranulation products, cytokines, reactive oxygen species and extracellular traps that are released during the process of neutrophil maturation or activation, could cause destruction to islet cells. In addition, these cells can initiate diabetogenic T cell response and promote type 1 diabetes development through cell–cell interactions with other immune and non‐immune cells. Furthermore, relevant antineutrophil therapies have been shown to delay and dampen the progression of insulitis and autoimmune diabetes. Here, we discuss the relationship between neutrophils and autoimmune type 1 diabetes from the aforementioned aspects to better understand the roles of these cells in the initiation and development of type 1 diabetes.

Angiogenic and Restorative Abilities of Human Mesenchymal Stem Cells Were Reduced Following Treatment With Serum From Diabetes Mellitus Type 2 Patients

“…Another interesting finding in our work was excessive affinity of diabetic hMSCs to HUVECs obtained by SPR analysis. It was previously determined that the natural order of expression of adhesion molecules such as MAC‐1, selectins, and integrins was disturbed in cells exposed to hyperglycemic conditions [Huang et al, ]. Another reason for the reduction of angiogenic capacity in diabetic hMSCs was a decrease in differentiation potential into ECs and pericytes which coincided with a reduction in the rate of Dil‐Ac‐LDL uptake [Rezabakhsh et al, ].…”

Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases

“…Different immune cells, such macrophages and dendritic and T cells, have been suggested to play crucial roles in type 1 diabetes pathogenesis [53–55]. The contribution of autoreactive T cells to the destruction of pancreatic β cells as a consequence of an immunologically mediated destruction of the pancreatic tissues has been proposed as the key pathogenic mechanisms in type 1 diabetes [56, 57].…”

Increased formation of neutrophil extracellular traps is associated with gut leakage in patients with type 1 but not type 2 diabetes

“…Clinical observations have indicated that circulating concentrations of zonulin and lipopolysaccharide (LPS), which can reflect the degree of gut permeability, are higher in diabetes patients than in healthy controls . Increased NET formation, along with neutropenia, may result primarily from a leaky gut, because the invasion of microorganisms can generate reactive oxygen species (ROS) and cause inflammation that can promote the abnormal activation of neutrophils . In addition, NET‐induced damage to intestinal epithelial and endothelial cells can aggravate gut leakage.…”

“…[9][10][11][12] Increased NET formation, along with neutropenia, 6 may result primarily from a leaky gut, because the invasion of microorganisms can generate reactive oxygen species (ROS) and cause inflammation that can promote the abnormal activation of neutrophils. 13,14 In addition, NET-induced damage to intestinal epithelial and endothelial cells 15 can aggravate gut leakage. In a previous study, we proved that the staphylococcal nuclease that effectively degraded NETs relieved inflammation of the small intestine in non-obese diabetic (NOD) mice.…”