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

Scherm, Martin G.; Daniel, Carolin

doi:10.3389/fendo.2020.606322

Cited by 16 publications

(12 citation statements)

References 160 publications

(168 reference statements)

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“…MiR-21 and miR-93 are involved in inflammatory and apoptotic signaling pathways and were found downregulated in PBMCs of T1DM patients, whereas miR-326, which targets significant modulators of the immune system-vitamin D receptor (VDR) and erythroblastosis virus E26 oncogenic homolog 1 (ETS-1)-was overexpressed in PBMCs of T1DM patients, further implicating the role of miRNAs in T1DM autoimmunity. MiR-15, miR-26 and miR-31 are also believed to alter T cell functions, as they are found overexpressed in pre-T1DM stages and have the capability of impairing T regulatory (Treg) cell survival [56,57].…”

Section: Role Of Mirnas In T1dmmentioning

confidence: 99%

“…Apart from interactions with auto-antibodies, miRNAs seem to be interrelated with several proinflammatory cytokines. Interleukin (IL) 1b and TNF-a were found to increase the expression of miR-21, miR-34 and miR-146, whereas miR-23 and miR-149, were downregulated when exposed to IL-1b and interferon (IFN) γ, consequently affecting β-cell apoptosis [48,56,57].…”

Section: Role Of Mirnas In T1dmmentioning

confidence: 99%

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Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature

Margaritis

Margioula–Siarkou

Giza

et al. 2021

IJMS

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Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs’ biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to β-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

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Section: Role Of Mirnas In T1dmmentioning

confidence: 99%

Section: Role Of Mirnas In T1dmmentioning

confidence: 99%

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature

Margaritis

Margioula–Siarkou

Giza

et al. 2021

IJMS

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“…Using miRNA sequencing of CD4 + T cells from peripheral blood of children with or without ongoing islet autoimmunity, we were able to identify several differentially regulated miRNAs and investigated three in more detail. Specifically, we focused on miRNAs that are predicted to target negative regulators of T cell activation and could therefore potentially inhibit Treg induction [reviewed in (29)(30)(31)].…”

Section: Mirna Targeting To Foster Tregs In Islet Autoimmunitymentioning

confidence: 99%

Antigen-Specific Treg Therapy in Type 1 Diabetes – Challenges and Opportunities

et al. 2021

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Regulatory T cells (Tregs) are key mediators of peripheral self-tolerance and alterations in their frequencies, stability, and function have been linked to autoimmunity. The antigen-specific induction of Tregs is a long-envisioned goal for the treatment of autoimmune diseases given reduced side effects compared to general immunosuppressive therapies. However, the translation of antigen-specific Treg inducing therapies for the treatment or prevention of autoimmune diseases into the clinic remains challenging. In this mini review, we will discuss promising results for antigen-specific Treg therapies in allergy and specific challenges for such therapies in autoimmune diseases, with a focus on type 1 diabetes (T1D). We will furthermore discuss opportunities for antigen-specific Treg therapies in T1D, including combinatorial strategies and tissue-specific Treg targeting. Specifically, we will highlight recent advances in miRNA-targeting as a means to foster Tregs in autoimmunity. Additionally, we will discuss advances and perspectives of computational strategies for the detailed analysis of tissue-specific Tregs on the single-cell level.

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“…129 In addition to the observed impairments in Treg cell induction, we provided evidence for impaired Treg cell stability contributing to the multiple layers of immune tolerance impairments during ongoing islet autoimmunity. 130 Therefore, targeting or delivery of T cell-specific miRNAs could contribute to the development of innovative antigen-specific immunotherapy 134 and thereby broaden the window of application for insulin immunotherapy closer to clinical disease.…”

Section: Genetic Optimization Of Insulin-specific Immunotherapymentioning

confidence: 99%

100 Years of insulin: Lifesaver, immune target, and potential remedy for prevention

Ziegler

Danne

Daniel

et al. 2021

Med

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In this review, we bring our personal experiences to showcase insulin from its breakthrough discovery as a life-saving drug 100 years ago to its uncovering as the autoantigen and potential cause of type 1 diabetes and eventually as an opportunity to prevent autoimmune diabetes. The work covers the birth of insulin to treat patients, which is now 100 years ago; the development of human insulin, insulin analogs, devices, and the way into automated insulin delivery; the realization that insulin is the primary autoimmune target of type 1 diabetes in children; novel approaches of immunotherapy using insulin for immune tolerance induction; the possible limitations of insulin immunotherapy; and an outlook on how modern vaccines could remove the need for another 100 years of insulin therapy. INSULIN SAVES LIVESThe birthday of insulin Studying medicine in his home town of Berlin, Germany, Thomas Danne was always fascinated by the story of insulin. It started in Berlin in 1869, when a medical student, Paul Langerhans, described in his dissertation the pancreatic islet cells named after him. 1 In 1909, de Meyer gave the name ''insulin'' to the unknown substance formed in Langerhans' islets. 2 In 1921, two Canadians, Frederick Banting, a surgeon with a vision but no formal research training, and Charles Best, a medicine student, made it happen. 3 The birthday of insulin on January 11, 1922, was also the beginning of pediatric diabetology, when 14-year-old Leonard Thompson, diagnosed with diabetes in 1919, was treated at Toronto General Hospital with the extract prepared by Banting and Best. However, the researchers considered it a complete failure, since the glucose decreased only from 440 to 320 mg/dL, ketones remained present, and the local outcome was sterile abscess in the buttocks. 4 James Collip refined the extraction progress, and on January 23-24, 1922, his extract normalized the glucose and made the ketones disappear. On February 5, 1922, Banting and Best published the article ''The internal secretion of the pancreas.'' 5 Banting and his boss and head of the laboratory, J.R.R. Macleod, were rewarded with the Nobel

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

Cited by 16 publications

References 160 publications

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature

Antigen-Specific Treg Therapy in Type 1 Diabetes – Challenges and Opportunities

100 Years of insulin: Lifesaver, immune target, and potential remedy for prevention

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