scholarly journals Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yangyang Li ◽  
Yu Liu ◽  
Cong-Qiu Chu
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Th17 Cells ◽  
Current Knowledge ◽  
Treg Cells ◽  
Protective Role ◽  
Islet Autoimmunity ◽  
Genetic And Environmental Factors

Type 1 diabetes (T1D) is an autoimmune disease which is characterized by progressive destruction of insulin producing pancreatic isletβcells. The risk of developing T1D is determined by both genetic and environmental factors. A growing body of evidence supports an important role of T helper type 17 (Th17) cells along with impaired T regulatory (Treg) cells in the development of T1D in animal models and humans. Alteration of gut microbiota has been implicated to be responsible for the imbalance between Th17 and Treg cells. However, there is controversy concerning a pathogenic versus protective role of Th17 cells in murine models of diabetes in the context of influence of gut microbiota. In this review we will summarize current knowledge about Th17 cells and gut microbiota involved in T1D and propose Th17 targeted therapy in children with islet autoimmunity to prevent progression to overt diabetes.

scholarly journals IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan Huang ◽  
Qiyuan Tan ◽  
Ningwen Tai ◽  
James Alexander Pearson ◽  
Yangyang Li ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Gut Microbiota ◽  
Spontaneous Diabetes ◽  
Nod Mice ◽  
Treg Cells ◽  
Diabetes Development

Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5+ NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in BDC2.5+ NOD mice by generating Il-10-deficient BDC2.5+ NOD mice (BDC2.5+Il-10-/- NOD mice). Our results showed that BDC2.5+Il-10-/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5+ NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. In vitro studies showed that the gut microbiota from BDC2.5+Il-10-/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5+ NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4+ T cells. Moreover, the pathogenicity of CD4+ T cells was much increased, and this significantly accelerated the development of diabetes when these CD4+ T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4+ T cells in BDC2.5+ NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development.

scholarly journals Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

2021 ◽  
Vol 9 (7) ◽  
pp. 1519
Author(s):  
Sonia R. Isaacs ◽  
Dylan B. Foskett ◽  
Anna J. Maxwell ◽  
Emily J. Ward ◽  
Clare L. Faulkner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Virus Detection ◽  
Detection Methods ◽  
Islet Autoimmunity ◽  
Comprehensive Overview ◽  
Drug Candidates

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, as well as mechanistic studies of virus-infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here, we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

scholarly journals The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 959 ◽  
Author(s):  
Jefferson Antônio Leite ◽  
Gabriela Pessenda ◽  
Isabel C. Guerra-Gomes ◽  
Alynne Karen Mendonça de Santana ◽  
Camila André Pereira ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Dna Sensor ◽  
Proinflammatory Response

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.

scholarly journals miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Martin G. Scherm ◽  
Isabelle Serr ◽  
Adam M. Zahm ◽  
Jonathan Schug ◽  
Saverio Bellusci ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell Activation ◽  
Pancreatic Beta Cells ◽  
Cell Activation ◽  
Clinical Symptoms ◽  
Mechanistic Model ◽  
Treg Cells ◽  
Islet Autoimmunity ◽  
Molecular Approaches

AbstractIn type 1 diabetes, the appearance of islet autoantibodies indicates the onset of islet autoimmunity, often many years before clinical symptoms arise. While T cells play a major role in the destruction of pancreatic beta cells, molecular underpinnings promoting aberrant T cell activation remain poorly understood. Here, we show that during islet autoimmunity an miR142-3p/Tet2/Foxp3 axis interferes with the efficient induction of regulatory T (Treg) cells, resulting in impaired Treg stability in mouse and human. Specifically, we demonstrate that miR142-3p is induced in islet autoimmunity and that its inhibition enhances Treg induction and stability, leading to reduced islet autoimmunity in non-obese diabetic mice. Using various cellular and molecular approaches we identify Tet2 as a direct target of miR142-3p, thereby linking high miR142-3p levels to epigenetic remodeling in Tregs. These findings offer a mechanistic model where during islet autoimmunity miR142-3p/Tet2-mediated Treg instability contributes to autoimmune activation and progression.

scholarly journals Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Alessia Alunno ◽  
Elena Bartoloni ◽  
Onelia Bistoni ◽  
Giuseppe Nocentini ◽  
Simona Ronchetti ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Lymphocytes ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Current Knowledge ◽  
Treg Cells ◽  
T Helper ◽  
Systemic Lupus ◽  
Target Organs

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed.

scholarly journals Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

2021 ◽  
Author(s):  
Sonia R Isaacs ◽  
Dylan B Foskett ◽  
Anna J Maxwell ◽  
Emily J Ward ◽  
Clare L Faulkner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Virus Detection ◽  
Detection Methods ◽  
Islet Autoimmunity ◽  
Comprehensive Overview ◽  
Drug Candidates

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

The crucial role of early-life gut microbiota in the development of type 1 diabetes

2020 ◽  
Author(s):  
He Zhou ◽  
Lin Sun ◽  
Siwen Zhang ◽  
Xue Zhao ◽  
Xiaokun Gang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Crucial Role ◽  
Early Life

255-LB: The Role of Th1, Th2, Th17, and Treg Cells in Various Clinical Phases of Type 1 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 255-LB
Author(s):  
BURCIN AYDIN OZGUR ◽  
SUZAN CINAR ◽  
DERYA OZTURK ◽  
ENDER COSKUNPINAR ◽  
ALI OSMAN GUROL ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Treg Cells
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