Retro-inverso D-peptides as a novel targeted immunotherapy for Type 1 diabetes.

Retro-inverso D-peptides as a novel targeted immunotherapy for Type 1 diabetes. J Autoimmun. 2020 Sep 17;:102543 Authors: Lombardi A, Concepcion E, Hou H, Arib H, Mezei M, Osman R, Tomer Y Abstract Over the past four decades, the number of people with Type 1 Diabetes (T1D) has increased by 4% per year, making it an important public health challenge. Currently, no curative therapy exists for T1D and the only available treatment is insulin replacement. HLA-DQ8 has been shown to present antigenic islet peptides driving the activation of CD4+ T-cells in T1D patients. Specifically, the insulin peptide InsB:9-23 activates self-reactive CD4+ T-cells, causing pancreatic beta cell destruction. The aim of the current study was to identify retro-inverso-d-amino acid based peptides (RI-D-peptides) that can suppress T-cell activation by blocking the presentation of InsB:9-23 peptide within HLA-DQ8 pocket. We identified a RI-D-peptide (RI-EXT) that inhibited InsB:9-23 binding to recombinant HLA-DQ8 molecule, as well as its binding to DQ8 expressed on human B-cells. RI-EXT prevented T-cell activation in a cellular antigen presentation assay containing human DQ8 cells loaded with InsB:9-23 peptide and murine T-cells expressing a human T-cell receptor specific for the InsB:9-23-DQ8 complex. Moreover, RI-EXT blocked T-cell activation by InsB:9-23 in a humanized DQ8 mice both ex vivo and in vivo, as shown by decreased production of IL-2 and IFN-γ and reduced lymphocy...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research

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CONCLUSION: In cSLE, PA is associated with more hospitalizations and aggressive immunotherapy use. Although lupus disease activity improved over time, patients' QoL neither improved over time nor differed by having other autoimmune disease. Prospective, case-control, long-term follow-up studies on cSLE are needed to validate our results. MESH KEY INDEXING TERMS: Pediatric systemic lupus erythematosus; Autoimmune diseases; Outcome assessment. PMID: 33016198 [PubMed - as supplied by publisher]
Source: Lupus - Category: Rheumatology Authors: Tags: Lupus Source Type: research
Authors: El-Mokhtar MA, Elsherbiny NM, Sayed D, Raafat DM, Askar E, Hussein A, Abdel-Malek MAY, Shalaby AM Abstract B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we ...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
ConclusionsThe current in vitro study provides strong evidence that PDLSCs seem to be a very promising source for overcoming the autoimmune destruction seen in T1D as they exerted an immunosuppressive effect on monocyte derived mDCs from patients with T1D. Additional studies should be conducted to further reveal the immunomodulatory and suppressive properties of PDLSCs and their potential use in immunotherapy for this disease.
Source: Journal of Diabetes and Metabolic Disorders - Category: Endocrinology Source Type: research
Type 1 diabetes is an autoimmune disease caused by the destruction of the insulin-producing β-cells. An ideal immunotherapy should combine the blockade of the autoimmune response with the recovery of functional target cell mass. With the aim to develop new therapies for type 1 diabetes that could contribute to β-cell mass restoration, a drug repositioning analysis based on systems biology was performed to identify the β-cell regenerative potential of commercially available compounds. Drug repositioning is a strategy used for identifying new uses for approved drugs that are outside the scope of the medical in...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Authors: Yap YA, Mariño E Abstract Diet-microbiota related inflammatory conditions such as obesity, autoimmune type 1 diabetes (T1D), type 2 diabetes (T2D), cardiovascular disease (CVD) and gut infections have become a stigma in Western societies and developing nations. This book chapter examines the most relevant pre-clinical and clinical studies about diet-gut microbiota approaches as an alternative therapy for diabetes. We also discuss what we and others have extensively investigated- the power of dietary short-chain fatty acids (SCFAs) technology that naturally targets the gut microbiota as an alternativ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Conclusions/interpretationCollectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management.
Source: Diabetologia - Category: Endocrinology Source Type: research
Immunotherapy has transformed the treatment landscape for a wide range of human cancers. Immune checkpoint inhibitors (ICIs), monoclonal antibodies that block the immune-regulatory “checkpoint” receptors CTLA-4, PD-1, or its ligand PD-L1, can produce durable responses in some patients. However, coupled with their success, these treatments commonly evoke a wide range of immune-related adverse events (irAEs) that can affect any organ system and can be treatment-limiting and life-threatening, such as diabetic ketoacidosis, which appears to be more frequent than initially described. The majority of irAEs from check...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Abstract Type 1 diabetes is an autoimmune disease caused by the immune-mediated destruction of pancreatic β cells that results in lifelong absolute insulin deficiency. For nearly a century, insulin replacement has been the only therapy for most people living with this disease. Recent advances in technology and our understanding of β cell development, glucose metabolism, and the underlying immune pathogenesis of the disease have led to innovative therapeutic and preventative approaches. A paradigm shift in immunotherapy development toward the targeting of islet-specific immune pathways involved in toleran...
Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab 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 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
Type 1 diabetes is an autoimmune disease characterized by loss of pancreatic beta cells and reliance on exogenous insulin for survival. It is one of the most common chronic diseases of childhood, and its incidence is increasing worldwide.1 Despite significant advances in insulin therapy, many patients fail to achieve satisfactory glycemic control, which leads to an increased risk of complications and reduced life expectancy.2
Source: Kidney International - Category: Urology & Nephrology Authors: Tags: Nephrology Digest Source Type: research
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