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

2021 ◽  
Vol 12 ◽  
Author(s):  
Isabelle Serr ◽  
Felix Drost ◽  
Benjamin Schubert ◽  
Carolin Daniel
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Cell Level ◽  
Tissue Specific ◽  
Self Tolerance ◽  
Specific Induction ◽  
Challenges And Opportunities ◽  
And Function ◽  
Mirna Targeting

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.

scholarly journals Thymus Dysfunction in the Development of Type 1 Diabetes and Endocrine Autoimmune Diseases

2009 ◽  
Vol 05 (0) ◽  
pp. 24
Author(s):  
Vincent Geenen ◽  
Olivier Dardenne ◽  
◽  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Autoimmune Response ◽  
Thymic Epithelial Cells ◽  
Self Tolerance ◽  
Genes Encoding ◽  
Organ Specific ◽  
Dominant Member ◽  
Large Repertoire

The discovery that thymic epithelium from many species expresses a large repertoire of genes encoding neuroendocrine and other tissuerestricted antigens has radically changed our knowledge of the pathogenic mechanisms underlying the development of organ-specific autoimmune diseases such as type 1 diabetes and autoimmune endocrine diseases. Rather than a breakdown of immunological selftolerance in periphery, there is mounting evidence that the diabetogenic autoimmune response may first arise from a thymus dysfunction in the central programming of β-cell self-tolerance. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin gene/protein family expressed in thymic epithelial cells (TECs) from different species, and Igf2-/- mice fail to programme complete tolerance to insulin. Based on the homology between insulin, the primary and immunogenic auto-antigen of type 1 diabetes, and IGF-2, the tolerogenic selfantigen of the insulin family, the design of a regulatory/negative self-vaccination for prevention against type 1 diabetes has been proposed and is under development.

scholarly journals Agent-Based Modeling of Immune Response to Study the Effects of Regulatory T Cells in Type 1 Diabetes

Processes ◽  
2018 ◽  
Vol 6 (9) ◽  
pp. 141
Author(s):  
Qian Xu ◽  
Mustafa Ozturk ◽  
Ali Cinar
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Pancreatic Tissue ◽  
Agent Based ◽  
Self Tolerance ◽  
And Function ◽  
Good Environment

Regulatory T cells (Tregs) have an important role in self-tolerance. Understanding the functions of Tregs is important for preventing or slowing the progress of Type 1 Diabetes. We use a two-dimensional (2D) agent-based model to simulate immune response in mice and test the effects of Tregs in tissue protection. We compared the immune response with and without Tregs, and also tested the effects of Tregs from different sources or with different functions. The results show that Tregs can inhibit the proliferation of effector T cells by inhibiting antigens presenting via dendritic cells (DCs). Although the number and function of Tregs affect the inhibition, a small number of Tregs compared to CD4+ T cells can effectively protect islets in pancreatic tissue. Finally, we added Tregs to the system in the middle phase of the immune response. The simulation results show that Tregs can inhibit the production of effector CD8+ T cells and maintain a good environment for β cell regeneration.

Features of the ovarian reserve of women of reproductive age suffering from autoimmune diseases

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. 27-30
Author(s):  
Elena N. Andreeva ◽  
Olga R. Grigoryan ◽  
Yulia S. Absatarova ◽  
Irina S. Yarovaya ◽  
Robert K. Mikheev
Keyword(s):  
Type 1 Diabetes ◽  
Thyroid Gland ◽  
Autoimmune Diseases ◽  
Ovarian Reserve ◽  
Reproductive Potential ◽  
Reproductive Age ◽  
Control Group ◽  
Antithyroid Antibodies ◽  
Healthy Women

The reproductive potential of a woman depends on indicators of the ovarian reserve, such as the anti-Muller hormone (AMH) and the number of antral follicles (NAF). Autoimmune diseases have a significant effect on fertility and contribute to the development of premature ovarian failure. Aim.To evaluate the parameters of the ovarian reserve in patients with type 1 diabetes mellitus, carriers of antibodies to the thyroid gland in a state of euthyroidism and compare them with similar parameters in healthy women. Materials and methods.In the first block of the study, the level of AMH, follicle-stimulating hormone, luteinizing hormone, NAF was studied among 224 women with diabetes and 230 healthy women in the control group. In block II, the level of the above hormonal indices was studied in 35 carriers of antithyroid antibodies in the state of euthyroidism and 35 healthy women. Results.In patients with type 1 diabetes, the level of AMH, NAF was statistically significantly lower when compared with the control group. Among carriers of antithyroid antibodies and healthy women, no difference in AMH and NAF was found. Conclusion.The autoimmune processes accompanying diabetes are more influenced by the ovarian reserve indices than autoimmune aggression to the tissues of the thyroid gland.

scholarly journals Diabetes Care, Glycemic Control, Complications, and Concomitant Autoimmune Diseases in Children with Type 1 Diabetes in Turkey: A Multicenter Study

2013 ◽  
Vol 5 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Gökşen Şimşek Damla ◽  
Aycan Zehra ◽  
Özen Samim ◽  
Çetinkaya Semra ◽  
Kara Cengiz ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Autoimmune Diseases ◽  
Multicenter Study ◽  
Diabetes Care

Characteristics of patients with type 1 diabetes and additional autoimmune disease in the DPV registry

2021 ◽  
Author(s):  
Nicole Prinz ◽  
Sascha R Tittel ◽  
Rainer Bachran ◽  
Robert Birnbacher ◽  
Joachim Brückel ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Diabetes Duration ◽  
Insulin Dosage ◽  
Insulin Regimen ◽  
Autoimmune Thyroid ◽  
Population Type ◽  
Multivariable Regression ◽  
Multivariable Regression Models

Abstract Context Autoimmune diseases affect ~8% of the population. Type 1 diabetes mellitus (T1DM) is linked to other autoimmune diseases (AID) like autoimmune thyroid disease, or Addison’s disease (AD) that may impact diabetes therapy and outcome. Objective To analyze demographic and clinical characteristics of other AID in T1DM from a large standardized registry, the prospective diabetes follow-up (DPV). Methods We searched the registry for T1DM with the additional diagnosis of Hashimoto’s thyroiditis (HT), Graves’ disease (GD), and/or AD. T1DM with other AID (n=6,166, 5.4%) were compared to isolated T1DM (n=107,457). For group comparisons, we used multivariable regression models with age, sex, diabetes duration, migration background, and type of insulin regimen as basic adjustments (microvascular endpoints: additionally adjusted for HbA1c). Results Patients with additional AID were more often female (54.7 vs. 32.0%, p<0.001) and had a longer diabetes duration (7.9 [4.2-12.5] vs. 6.7 [2.7-12.9] years, p<0.001). After adjustment, daily insulin dosage was higher in AD and HT compared to isolated T1DM (0.858±0.032 and 0.813±0.005 vs. 0.793±0.001 IU/kg*d). Retinopathy was less common in HT (1.5%), whereas it was more frequent in GD (3.1%) if compared to isolated T1DM (1.8%). In both GD and HT, microalbuminuria occurred less often (10.6% and 14.3% vs. 15.5%) and neuropathy (2.1% and 1.8% vs. 0.8%) was more common compared to isolated T1DM. Conclusions T1DM with additional AID show heterogeneous differences compared to isolated T1DM. T1DM plus AD or HT requires more insulin. Further, the rate of neuropathy is higher in HD or GD, whereas the rate of microalbuminuria is lower.

Physical Activity and Nerve Structure and Function in Patients With Longstanding Type 1 Diabetes

2021 ◽  
Vol 45 (7) ◽  
pp. S7
Author(s):  
Evan Lewis ◽  
Leif Erik Lovblom ◽  
Sebastien Lanctot ◽  
Daniel Scarr ◽  
Vera Bril ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 1 Diabetes ◽  
Structure And Function ◽  
Nerve Structure ◽  
And Function

Endocrine autoimmunity

2011 ◽  
pp. 34-44 ◽  
Author(s):  
Matthew J. Simmonds ◽  
Stephen C. L. Gough
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
Immune System ◽  
Endocrine System ◽  
Graves Disease ◽  
Self Tolerance ◽  
Autoimmune Attack ◽  
Endocrine Organs

Dysfunction within the endocrine system can lead to a variety of diseases with autoimmune attack against individual components being some of the most common. Endocrine autoimmunity encompasses a spectrum of disorders including, e.g., common disorders such as type 1 diabetes, Graves’ disease, Hashimoto’s thyroiditis, and rarer disorders including Addison’s disease and the autoimmune polyendocrine syndromes type 1 (APS 1) and type 2 (APS 2) (see Table 1.6.1). Autoimmune attack within each of these diseases although aimed at different endocrine organs is caused by a breakdown in the immune system’s ability to distinguish between self and nonself antigens, leading to an immune response targeted at self tissues. Investigating the mechanisms behind this breakdown is vital to understand what has gone wrong and to determine the pathways against which therapeutics can be targeted. Before discussing how self-tolerance fails, we first have to understand how the immune system achieves self-tolerance.

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