scholarly journals miRNA-Mediated Immune Regulation in Islet Autoimmunity and Type 1 Diabetes

2020 ◽  
Vol 11 ◽  
Author(s):  
Martin G. Scherm ◽  
Carolin Daniel
Keyword(s):  
Immune Regulation ◽  
Islet Autoimmunity ◽  
Physiological Processes ◽  
Individual Mirnas ◽  
Promising Target ◽  
And Function ◽  
Improved Methods ◽  
Specific Impact

The important role of microRNAs as major modulators of various physiological processes, including immune regulation and homeostasis, has been increasingly recognized. Consequently, aberrant miRNA expression contributes to the defective regulation of T cell development, differentiation, and function. This can result in immune activation and impaired tolerance mechanisms, which exert a cardinal function for the onset of islet autoimmunity and the progression to T1D. The specific impact of miRNAs for immune regulation and how miRNAs and their downstream targets are involved in the pathogenesis of islet autoimmunity and T1D has been investigated recently. These studies revealed that increased expression of individual miRNAs is involved in several layers of tolerance impairments, such as inefficient Treg induction and Treg instability. The targeted modulation of miRNAs using specific inhibitors, resulting in improved immune homeostasis, as well as improved methods for the targeting of miRNAs, suggest that miRNAs, especially in T cells, are a promising target for the reestablishment of immune tolerance.

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 A Triple Threat? The Role of Diet, Nutrition, and the Microbiota in T1D Pathogenesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Emma E. Hamilton-Williams ◽  
Graciela L. Lorca ◽  
Jill M. Norris ◽  
Jessica L. Dunne
Keyword(s):  
Beta Cell ◽  
Intestinal Microbiota ◽  
Beta Cell Function ◽  
Cell Function ◽  
The Body ◽  
Islet Autoimmunity ◽  
Potential Mechanism ◽  
Modifiable Factors ◽  
And Function

In recent years the role of the intestinal microbiota in health and disease has come to the forefront of medical research. Alterations in the intestinal microbiota and several of its features have been linked to numerous diseases, including type 1 diabetes (T1D). To date, studies in animal models of T1D, as well as studies in human subjects, have linked several intestinal microbiota alterations with T1D pathogenesis. Features that are most often linked with T1D pathogenesis include decreased microbial diversity, the relative abundance of specific strains of individual microbes, and altered metabolite production. Alterations in these features as well as others have provided insight into T1D pathogenesis and shed light on the potential mechanism by which the microbiota plays a role in T1D pathogenesis, yet the underlying factors leading to these alterations remains unknown. One potential mechanism for alteration of the microbiota is through diet and nutrition. Previous studies have shown associations of diet with islet autoimmunity, but a direct contributing factor has yet to be identified. Diet, through introduction of antigens and alteration of the composition and function of the microbiota, may elicit the immune system to produce autoreactive responses that result in the destruction of the beta cells. Here, we review the evidence associating diet induced changes in the intestinal microbiota and their contribution to T1D pathogenesis. We further provide a roadmap for determining the effect of diet and other modifiable factors on the entire microbiota ecosystem, including its impact on both immune and beta cell function, as it relates to T1D. A greater understanding of the complex interactions between the intestinal microbiota and several interacting systems in the body (immune, intestinal integrity and function, metabolism, beta cell function, etc.) may provide scientifically rational approaches to prevent development of T1D and other childhood immune and allergic diseases and biomarkers to evaluate the efficacy of interventions.

scholarly journals The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1748 ◽  
Author(s):  
Arianna Bettiga ◽  
Francesco Fiorio ◽  
Federico Di Marco ◽  
Francesco Trevisani ◽  
Annalisa Romani ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Advanced Glycation End Products ◽  
Cell Function ◽  
Advanced Glycation ◽  
Covalent Bonds ◽  
Physiological Processes ◽  
Glycation End Products ◽  
End Products ◽  
And Function

Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.

scholarly journals Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium

2017 ◽  
Vol 58 (1) ◽  
pp. R1-R13 ◽  
Author(s):  
Gillian A Gray ◽  
Christopher I White ◽  
Raphael F P Castellan ◽  
Sara J McSweeney ◽  
Karen E Chapman
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Systemic Corticosteroid ◽  
Physiological Function ◽  
Pressure Overload ◽  
Hydroxysteroid Dehydrogenase ◽  
And Function ◽  
Glucocorticoid Metabolism

Corticosteroids influence the development and function of the heart and its response to injury and pressure overload via actions on glucocorticoid (GR) and mineralocorticoid (MR) receptors. Systemic corticosteroid concentration depends largely on the activity of the hypothalamic–pituitary–adrenal (HPA) axis, but glucocorticoid can also be regenerated from intrinsically inert metabolites by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), selectively increasing glucocorticoid levels within cells and tissues. Extensive studies have revealed the roles for glucocorticoid regeneration by 11β-HSD1 in liver, adipose, brain and other tissues, but until recently, there has been little focus on the heart. This article reviews the evidence for glucocorticoid metabolism by 11β-HSD1 in the heart and for a role of 11β-HSD1 activity in determining the myocardial growth and physiological function. We also consider the potential of 11β-HSD1 as a therapeutic target to enhance repair after myocardial infarction and to prevent the development of cardiac remodelling and heart failure.

scholarly journals The critical role of Krüppel-like factors in kidney disease

2017 ◽  
Vol 312 (2) ◽  
pp. F259-F265 ◽  
Author(s):  
Sandeep K. Mallipattu ◽  
Chelsea C. Estrada ◽  
John C. He
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Vital Role ◽  
Glomerular Filtration Barrier ◽  
Kidney Fibrosis ◽  
Physiological Processes ◽  
Filtration Barrier ◽  
And Function ◽  
Mammalian Embryonic Development

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct. This review highlights our current knowledge of KLFs in the kidney, which includes their pattern of expression and their function in regulating key biological processes. We will also critically examine the currently available literature on KLFs in the kidney and offer some key areas in need of further investigation.

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.

scholarly journals Serine protease inhibitors and human wellbeing interplay: new insights for old friends

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7224 ◽  
Author(s):  
Héla Mkaouar ◽  
Nizar Akermi ◽  
Aicha Kriaa ◽  
Anne-Laure Abraham ◽  
Amin Jablaoui ◽  
...  
Keyword(s):  
Serine Protease ◽  
Protease Inhibitors ◽  
Structural Data ◽  
Ecological Niches ◽  
Serine Protease Inhibitors ◽  
New Therapeutic Approaches ◽  
Physiological Processes ◽  
Health And Disease ◽  
And Function

Serine Protease Inhibitors (Serpins) control tightly regulated physiological processes and their dysfunction is associated to various diseases. Thus, increasing interest is given to these proteins as new therapeutic targets. Several studies provided functional and structural data about human serpins. By comparison, only little knowledge regarding bacterial serpins exists. Through the emergence of metagenomic studies, many bacterial serpins were identified from numerous ecological niches including the human gut microbiota. The origin, distribution and function of these proteins remain to be established. In this report, we shed light on the key role of human and bacterial serpins in health and disease. Moreover, we analyze their function, phylogeny and ecological distribution. This review highlights the potential use of bacterial serpins to set out new therapeutic approaches.

scholarly journals Sophisticated Gene Regulation for a Complex Physiological System: The Role of Non-coding RNAs in Photoreceptor Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Sabrina Carrella ◽  
Sandro Banfi ◽  
Marianthi Karali
Keyword(s):  
Molecular Mechanisms ◽  
Developmental Process ◽  
Photoreceptor Cells ◽  
Sensory Transduction ◽  
Circular Rnas ◽  
Therapeutic Implications ◽  
Physiological Processes ◽  
Non Coding Rnas ◽  
And Function

Photoreceptors (PRs) are specialized neuroepithelial cells of the retina responsible for sensory transduction of light stimuli. In the highly structured vertebrate retina, PRs have a highly polarized modular structure to accommodate the demanding processes of phototransduction and the visual cycle. Because of their function, PRs are exposed to continuous cellular stress. PRs are therefore under pressure to maintain their function in defiance of constant environmental perturbation, besides being part of a highly sophisticated developmental process. All this translates into the need for tightly regulated and responsive molecular mechanisms that can reinforce transcriptional programs. It is commonly accepted that regulatory non-coding RNAs (ncRNAs), and in particular microRNAs (miRNAs), are not only involved but indeed central in conferring robustness and accuracy to developmental and physiological processes. Here we integrate recent findings on the role of regulatory ncRNAs (e.g., miRNAs, lncRNAs, circular RNAs, and antisense RNAs), and of their contribution to PR pathophysiology. We also outline the therapeutic implications of translational studies that harness ncRNAs to prevent PR degeneration and promote their survival and function.

scholarly journals Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years

2020 ◽  
Vol 105 (12) ◽  
pp. e4638-e4651 ◽  
Author(s):  
Petra M Pöllänen ◽  
Samppa J Ryhänen ◽  
Jorma Toppari ◽  
Jorma Ilonen ◽  
Paula Vähäsalo ◽  
...  
Keyword(s):  
Glutamate Decarboxylase ◽  
Seroconversion Rate ◽  
Disease Process ◽  
Islet Autoantibodies ◽  
Islet Autoimmunity ◽  
Prolonged Delay ◽  
Islet Antigen

Abstract Context We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A– and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01). Conclusions In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.

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