Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes

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The histological analysis of human pancreatic samples in type 1 diabetes (T1D) has been proven essential to move forward in the evaluation of in situ events characterizing T1D. Increasing availability of pancreatic tissues collected from diabetic multiorgan donors by centralized biorepositories, which have shared tissues among researchers in the field, has allowed a deeper understanding of T1D pathophysiology, using novel immunohistological and high-throughput methods. In this review, we provide a comprehensive update of the main recent advancements in the characterization of cellular and molecular events involving endocrine and exocrine pancreas as well as the immune system in the onset and progression of T1D. Additionally, we underline novel elements, which provide evidence that T1D pathological changes affect not only islet β-cells but also the entire pancreas.

Section: Innate Immune Cells: Novel Players In T1d Pathogenesismentioning

confidence: 65%

Section: Exocrine Pancreas In T1d: Not Just a Matter Of Islet Cellsmentioning

confidence: 94%

Section: Innate Immune Cells: Novel Players In T1d Pathogenesismentioning

confidence: 99%

Section: Insights Into T1d Pathogenesis: Major Contribution From Tissmentioning

confidence: 99%

Section: Innate Immune Cells: Novel Players In T1d Pathogenesismentioning

confidence: 99%

See 3 more Smart Citations

From immunohistological to anatomical alterations of human pancreas in type 1 diabetes: New concepts on the stage

Nigi

Maccora

Dotta

et al. 2019

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Innate immunity in latent autoimmune diabetes in adults

Hao

Pearson

Wong

et al. 2021

Latent autoimmune diabetes in adults (LADA) is an autoimmune disease that shares some genetic, immunological and clinical features with both type 1 diabetes and type 2 diabetes. Immune cells including CD4 + T cells, CD8 + T cells, B cells, macrophages and dendritic cells (DCs) have been detected in the pancreas of patients with LADA and a rat model of LADA. Therefore, similar to type 1 diabetes, the pathogenesis of LADA may be caused by interactions between islet β-cells and innate and adaptive immune cells. However, the role of the immunity in the initiation and progression of LADA remains largely unknown. In this review, we have summarized the potential roles of innate immunity and immune-modulators in LADA development. Furthermore, we have examined the evidence and discussed potential innate immunological reasons for the slower development of LADA compared with type 1 diabetes. More in-depth mechanistic studies are needed to fully elucidate the roles of innate immune-associated genes, molecules and cells in their contributions to LADA pathogenesis. Undertaking these studies will greatly enhance the development of new strategies and optimization of current strategies for the diagnosis and treatment of the disease. K E Y W O R D Sautoimmune, diabetes mellitus, innate immune cells, innate immunity, latent autoimmune diabetes in adults | INTRODUCTIONLatent autoimmune diabetes in adults (LADA), also known as type 1.5 diabetes or slow-onset diabetes in adults, is an autoimmune disease that shares some genetic, immunological and clinical features with both type 1 diabetes and type 2 diabetes. [1][2][3][4][5] The disease was first described in 1983 6 and was defined as LADA in 1993. 7 Although LADA accounts for approximately 1.5%-14.2% of the type 2 diabetes population, 8-14 no unified criteria or management guidelines have existed for LADA. Recently, a panel of international experts defined a strategy for LADA management, which will be greatly helpful to the diagnosis and treatment of the disease in clinical practice. 15 GADA level is considered as the most valuable discriminatory parameter to predict the development of β-cell function in LADA. 16 Compared with low level of glutamic acid decarboxylase antibody (GADA), high level of GADA in LADA is associated with faster insulin progression, indicating that the presence of high level of GADA was a significant predictor of insulin requirement in LADA. 17 Our group also found that patients with high level of GADA showed a worse baseline and accelerated decline of β-cell function, 18 while the metabolic phenotypes and β-cell function in LADA patients with a low level of GADA were similar to that in type 2 diabetes patients. 19 It was reported that the presence of N-terminally truncated GAD65 autoantibody in individuals with adult-onset diabetes is associated with the clinical

Neutrophils and their role in the aetiopathogenesis of type 1 and type 2 diabetes

Giovenzana

Carnovale

Phillips

et al. 2021

Multiple and complex aetiological processes underlie diabetes mellitus, which invariably result in the development of hyperglycaemia. Although there are two prevalent distinct forms of the disease, that is, type 1 and type 2 diabetes, accumulating evidence indicates that these syndromes share more aetiopathological mechanisms than originally thought. This compels a rethinking of the approaches to prevent and treat the different manifestations of what eventually becomes a hyperglycaemic state. This review aims to address the involvement of neutrophils, the most abundant type of granulocytes involved in the initiation of the acute phase of inflammation, in the aetiopathogenesis of diabetes mellitus, with a focus on type 1 and type 2 diabetes. We review the evidence that neutrophils are the first leucocytes to react to and accumulate inside target tissues of diabetes, such as the pancreas and insulin-sensitive tissues. We then review available data on the role of neutrophils and their functional alteration, with a focus on NETosis, in the progression towards clinical disease. Finally, we review potential approaches as secondary and adjunctive treatments to limit neutrophil-mediated damage in the prevention of the progression of subclinical disease to clinical hyperglycaemia.