Innate Viral Receptor Signaling Determines Type 1 Diabetes Onset

Morse, Zachary J.; Horwitz, Marc S.

doi:10.3389/fendo.2017.00249

Cited by 23 publications

(23 citation statements)

References 107 publications

(121 reference statements)

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“…Other beneficial effects of E2 on innate immunity were observed with Coxsackievirus-infected human islets in which E2 produced a profound decrease in the synthesis of the chemokine CXCL10 [49] . There is a wealth of evidence demonstrating an association of T1D onset with enteroviral infections [50] , [51] . The ability of E2 to decrease CXCL10 synthesis is significant since this pro-inflammatory chemokine can recruit autoreactive T cells into the islets to propagate β cell destruction [52] .…”

Section: Islet and Immune Cell Interactionsmentioning

confidence: 99%

Sex differences underlying pancreatic islet biology and its dysfunction

Gannon

Kulkarni

Tse

et al. 2018

Molecular Metabolism

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BackgroundThe sex of an individual affects glucose homeostasis and the pathophysiology, incidence, and prevalence of diabetes as well as the response to therapy.Scope of the reviewThis review focuses on clinical and experimental sex differences in islet cell biology and dysfunction during development and in adulthood in human and animal models. We discuss sex differences in β-cell and α-cell function, heterogeneity, and dysfunction. We cover sex differences in communication between gonads and islets and islet-cell immune interactions. Finally, we discuss sex differences in β-cell programming by nutrition and other environmental factors during pregnancy.Major conclusionsImportant sex differences exist in islet cell function and susceptibility to failure. These differences represent sex-related biological factors that can be harnessed for gender-based prevention of and therapy for diabetes.

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Section: Islet and Immune Cell Interactionsmentioning

confidence: 99%

Sex differences underlying pancreatic islet biology and its dysfunction

Gannon

Kulkarni

Tse

et al. 2018

Molecular Metabolism

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“…Thus, multiple players may be involved in each case . Infection by enteroviruses (EVs) has been closely associated with the onset of T1D and is considered as a critical etiologic factor …”

Section: Introductionmentioning

confidence: 99%

Vitamin D status, enterovirus infection, and type 1 diabetes in Italian children/adolescents

et al. 2018

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At the time of the clinical onset of type 1 diabetes (T1D), we investigated 82 pediatric cases in parallel with 117 non-diabetic controls matched by age, geographic area, and time of collection. The occurrence of an enteroviral infection was evaluated in peripheral blood using a sensitive method capable of detecting virtually all human enterovirus (EV) types. While non-diabetic controls were consistently EV-negative, 65% of T1D cases carried EVs in blood. The vitamin D status was assessed by measuring the concentration of 25-hydroxyvitamin D [25(OH)D] in serum. Levels of 25(OH)D were interpreted as deficiency (≤50 nmol/L), insufficiency (52.5-72.5 nmol/L), and sufficiency (75-250 nmol/L). In T1D cases, the median serum concentration of 25(OH)D was 54.4 ± 27.3 nmol/L vs 74.1 ± 28.5 nmol/L in controls (P = .0001). Diabetic children/adolescents showed deficient levels of vitamin D 25(OH)D (ie, 72.5 nmol/L) in 48.8% cases vs 17.9% in non-diabetic controls (P = .0001). Unexpectedly, the median vitamin D concentration was significantly reduced in virus-positive vs virus-negative diabetics (48.2 ± 22.5 vs 61.8 ± 31.2 nmol/L; P = .015), with deficient levels in 58.5% vs 31.0%, respectively. Thus, at the time of clinical onset, EV-positive cases had reduced vitamin D levels compared with EV-negative cases. This could indicate either that the virus-negative children/adolescents had been hit by a non-infectious T1D-triggering event, or that children/adolescents with proper levels of vitamin D had been able to rapidly clear the virus. Thus, it would be important to assess whether adequate vitamin D supplementation before or during the prediabetic phase of T1D may counteract the diabetogenic potential of infectious pathogens.

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“…One of the most common mechanisms proposed in autoimmunity is an innate immune cell hyper-activation, such as dendritic cells (DC), that can overstimulate T lymphocytes (Di Marco et al, 2018). TLR7/8 activation in DC triggers the release of pro-inflammatory cytokines (Morse and Horwitz, 2017;Salvi et al, 2018) and immune cells intercellular interactions, resulting in expanded T-cell-clones and auto-immune risk phenotype, in both mice and humans (Ara et al, 2018;Morawski and Bolland, 2018). The TLR7/8 activation of the downstream immune system and auto-immune risk phenotype contributes to beta-cell destruction, promotes diabetes development, and causes T-cell exhaustion (Lee et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes

Tesovnik

Kovač

Pohar

et al. 2020

Front. Cell Dev. Biol.

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Extracellular vesicles with their molecular cargo can modulate target cell response and may affect the pathogenesis of diseases. The extracellular vesicles containing micro-RNAs (miRNAs), which are often studied as disease biomarkers, but rarely as mediators of the disease development. The role of extracellular vesicles derived miRNAs in type 1 diabetes is currently not well established. We observed a fraction of blood plasma extracellular vesicles positive for membrane proteins potentially associated with insulinproducing beta-cells and identified differentially expressed extracellular vesicles derived miRNAs in individuals with type 1 diabetes. These differentially expressed extracellular vesicles derived human miRNAs in participants with type 1 diabetes and participants with Langerhans islets beta-cells destruction showed the ability to activate TLR7/8 signaling cascade and increase activation as well as cytotoxicity of the effector blood immune cells with cytokine and chemokine release. Our results illustrate extracellular vesicles derived human miRNAs as modulators of the immune system in type 1 diabetes autoimmunity, providing potentially new insight into the pathogenesis of the disease, and novel molecular targets for intervention and type 1 diabetes prevention.

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Innate Viral Receptor Signaling Determines Type 1 Diabetes Onset

Cited by 23 publications

References 107 publications

Sex differences underlying pancreatic islet biology and its dysfunction

Sex differences underlying pancreatic islet biology and its dysfunction

Vitamin D status, enterovirus infection, and type 1 diabetes in Italian children/adolescents

Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes

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