Targeting Stem Cell-Derived Tissue-Associated Regulatory T Cells for Type 1 Diabetes Immunotherapy

AbstractPurpose of ReviewType 1 diabetes (T1D) is an autoimmune disease in which the immune cells selectively destroy the pancreatic beta ( β) cells and results in the deficiency of insulin production. The optimal treatment strategy for T1D should be preventing of β-cell destruction in the pancreas. The purpose of this review is to discuss the immunological therapeutic mechanisms that will help to understand the development and contro l of β-cell destruction. The review also presents a novel method for development of autoantigen (Ag)-specific regulatory T cells (Tregs) for T1D immunotherapy.Recent FindingsPancreatic-resident Tregs have the ability to dramatically suppress hyperactive immune cells. Islet cell transplantation is another attractive approach to replace the failed β cells. Due to the limited source of islet cells, research is going on in the use of animal cells and adult stem cells that may be derived from the patient’s own body to produce β cells for transplantation.SummaryThe mechanism behind the pancreatic β-cell destruction is largely unknown. In this review, a novel approach for the generation of tissue-associated Tregs from stem cells is considered. The stem cell-derived tissue-associated Tregs have the ability to home to the damaged pancreas to prevent the destruction. The review also provides ne w insights on the mechanism on how these suppressive immune cells protect the pancreas from the destruction of autoimmune cells...
Source: Current Diabetes Reports - Category: Endocrinology Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our analysis implicates the autoimmune PTPN22 rs2476601 risk allele A in controlling the frequency of Tregs in human peripheral blood. This article is protected by copyright. All rights reserved. PMID: 31808541 [PubMed - as supplied by publisher]
Source: European Journal of Immunology - Category: Allergy & Immunology Authors: Tags: Eur J Immunol Source Type: research
CONCLUSIONS: At adolescence, both Crohn's disease and ulcerative colitis are associated with multiple comorbidities, not limited to autoimmune disorders. PMID: 31801156 [PubMed - as supplied by publisher]
Source: Pediatric Research - Category: Pediatrics Authors: Tags: Pediatr Res Source Type: research
ath M Abstract IL-6 is a pro-inflammatory cytokine upregulated in some autoimmune diseases. The role of IL-6 in the development of type 1 diabetes (T1D) is unclear. Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D. However, in some rodent models and isolated human islets, IL-6 has been found to have a protective role for beta cells by reducing oxidative stress. Hence, we systematically investigated local tissue expression of IL-6 in human pancreas from non-diabetic, auto-antibody positive donors and donors with ...
Source: Clinical Immunology - Category: Allergy & Immunology Authors: Tags: Clin Immunol Source Type: research
This study demonstrates for the first time that senescent cells secrete functional LTs, significantly contributing to the LTs pool known to cause or exacerbate idiopathic pulmonary fibrosis. Against Senolytics https://www.fightaging.org/archives/2019/11/against-senolytics/ There is no consensus in science that is so strong as to have no heretics. So here we have an interview with a naysayer on the matter of senolytic treatments, who argues that the loss of senescent cells in aged tissues will cause more harm to long-term health than the damage they will do by remaining. To be clear, I think this to be a ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
BO Abstract Induction of antigen-specific regulatory T cells (Tregs) in vivo is the holy grail of current immune-regulating therapies in autoimmune diseases, such as type 1 diabetes. Tolerogenic dendritic cells (tolDCs) generated from monocytes by a combined treatment with vitamin D and dexamethasone (marked by CD52hi and CD86lo expression) induce antigen-specific Tregs. We evaluated the phenotypes of these Tregs using high-dimensional mass cytometry to identify a surface-based T cell signature of tolerogenic modulation. Naïve CD4+ T cells were stimulated with tolDCs or mature inflammatory DCs pulsed with pr...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research
Abstract Regulatory T cells (Tregs) play a central role in the induction and maintenance of immune homeostasis and self-tolerance. Tregs constantly express the high-affinity receptor to IL-2. IL-2 is a pleiotropic cytokine and a key survival factor for Tregs. It maintains Tregs' suppressive function by promoting Foxp3 expression and subsequent production of immunoregulatory cytokines. Administration of low-dose IL-2 is shown to be a promising approach to prevent allograft rejection and to treat autoimmune and inflammatory conditions in experimental models. The combination of IL-2 with its mAb (JES6-1) has also bee...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research
Senescent cells are a cause of aging, and much of the present focus in the study of cellular senescence is thus on targeting and destroying these unwanted cells in order to treat aging. However, a comparatively recent and intriguing finding is that at least some autoimmune diseases, such as type 1 diabetes, involve cellular senescence. The question at present is whether or not this true for all forms of autoimmunity. An autoimmune condition must have a trigger, something that prompts the immune system to attack healthy tissues, and it is possible that many different triggers converge on the generation of senescent c...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Conclusions/interpretationThis study provides a proof of principle for the use of iPSC-derived immune cells for modelling key cellular interactions in human type 1 diabetes.
Source: Diabetologia - Category: Endocrinology Source Type: research
Conclusions: Patients require careful long-term follow-up after DIHS/DRESS. Involvement of endocrine glands, especially FT1DM, should always be monitored in patients with a history of DIHS/DRESS. This study indicated that DIHS/DRESS could lead to APS, especially APS III, providing novel insights into the etiological factors of APS. PMID: 31687021 [PubMed]
Source: International Journal of Endocrinology - Category: Endocrinology Tags: Int J Endocrinol Source Type: research
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