Vaccination with a co‐expression DNA plasmid containing GAD65 fragment gene and IL‐10 gene induces regulatory CD4<sup>+</sup> T cells that prevent experimental autoimmune diabetes

Liu, Xinyuan; Zhang, Song; Li, Xia; Zheng, Peilin; Hu, Fang; Zhou, Zhiguang

doi:10.1002/dmrr.2780

Cited by 24 publications

(15 citation statements)

References 57 publications

(73 reference statements)

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“…CD4 + CD25 + Foxp3 + Treg cells have recently been considered as powerful mediators to re-balance of Th1/Th2 in autoimmune diabetes ( Liu et al, 2016 ). Moreover, Saunders et al (2007) showed that T. spiralis infection delays the onset and prevents the progression of T1DM.…”

Section: Trichinella -Derived Molecules: a Panacea For Moder...mentioning

confidence: 99%

Trichinella-induced immunomodulation: Another tale of helminth success

Bruschi

Ashour

Othman

2022

Food and Waterborne Parasitology

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Section: Trichinella -Derived Molecules: a Panacea For Moder...mentioning

confidence: 99%

Trichinella-induced immunomodulation: Another tale of helminth success

Bruschi

Ashour

Othman

2022

Food and Waterborne Parasitology

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“…An important insight from these studies is the observation that the secreted version of the polypeptide containing all epitopes has therapeutic benefit, but not the version in which peptides are targeted intracellularly. On the one hand, this is reminiscent of another DNA vaccine study in which the long GAD65190-315 peptide was more protective when secreted than the full non-secreted GAD65 protein in NOD mice (40). On the other hand, we have shown that both secreted and non-secreted forms induced immune responses in draining lymph nodes (23).…”

Section: Discussionmentioning

confidence: 61%

Preclinical evaluation of a precision medicine approach to DNA vaccination in Type 1 diabetes

Creusot

2021

Preprint

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Antigen-specific immunotherapy involves the delivery of self-antigens as proteins or peptides (or using nucleic acids encoding them) to be presented with the goal of inducing tolerance. Approaches employing specific epitopes restricted to the subject's MHC haplotypes have multiplied and offer a more focused and tailored way of targeting autoreactive T cells. In addition, the Endotope platform allows endogenously expressed epitopes to be processed and presented on appropriate MHC class I and II molecules. Here, we evaluated the efficacy of a DNA vaccine encoding epitopes selected and tailored for the non-obese diabetic (NOD) mouse compared to the expression of the proinsulin protein, one of the most successful antigens in prevention of NOD disease, and we assessed the influence of several parameters (e.g. route, dosing frequency) on preventing diabetes onset at normoglycemic and dysglycemic stages. First, encoded peptides should be secreted for effective disease prevention. Furthermore, short weekly treatments with Endotope and proinsulin DNA vaccines delay disease onset, but sustained treatments are required for long-term protection, which was more significant with intradermal delivery. Although epitopes can be presented for at least two weeks, reducing the frequency of antigen administration from weekly to every other week reduced efficacy. Finally, both Endotope and proinsulin DNA vaccines were effective in the dysglycemic stage of disease, but proinsulin provided better protection, particularly in subjects with slower progression of disease. Thus, our data support the possibility of applying a precision medicine approach based on tailored epitopes for the treatment of tissue-specific autoimmune diseases with DNA vaccines.

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“…To verify that IL16 could regulate the infiltration of CD4+ CD25+ Foxp3+ Tregs, we used recombinant IL16 to stimulate lymphocytes. IL10 is known to significantly increase the number of CD4+ CD25+ Tregs [ 26 ]. Therefore, lymphocytes were stimulated with recombinant IL10 as the positive control group.…”

Section: Resultsmentioning

confidence: 99%

microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer

et al. 2021

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Previous studies have confirmed that microRNA (miR)-128-3p is expressed at low levels in gastric cancer (GC), and low miR-128-3p expression promotes the growth of GC cells. However, whether the dysregulation of miR-128-3p expression affects tumor-infiltrating lymphocytes (TILs) and leads to immune escape remains unclear. In the present study, predictive bioinformatics approaches showed that miR-128-3p expression was inversely correlated with tumor-infiltrating lymphocyte enrichment. When CD4 + T cells and regulatory T cells (Tregs) were enriched, lower miR-128-3p expression was associated with worse overall survival. However, when numbers of CD8 + T cells were decreased, the upregulation of miR-128-3p expression had a favorable effect on GC prognosis. Dual-luciferase reporter assays and cell biology experiments revealed that interleukin 16 (IL16) was the target of miR-128-3p and was negatively regulated by miR-128-3p. In addition, GC cells were cocultured with T lymphocytes, and the subsequent flow cytometric analysis showed that overexpression of miR-128-3p in tumor cells decreased the percentages of CD4+ CD25+ Foxp3+ Tregs by downregulating IL16 expression in GC, whereas miR-128-3p inhibition had the opposite effect. Moreover, the recombinant IL16 reversed the effects of miR-128-3p overexpression, and a competitive antibody against the IL16 receptor CD4 also reversed the effects of miR-128-3p knockdown. These studies identified the mechanism by which the miR-128-3p/IL16 axis promotes the infiltration of CD4+ Tregs in GC, and this mechanism will be a promising therapeutic target in GC immunotherapy.

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Vaccination with a co‐expression DNA plasmid containing GAD65 fragment gene and IL‐10 gene induces regulatory CD4⁺ T cells that prevent experimental autoimmune diabetes

Abstract: Our data suggested that SGAD65190-315 /IL-10 DNA vaccine had protective effects on T1D by upregulating autoantigen-reactive Tregs. Our findings may provide a novel preventive therapy for T1D. Copyright © 2016 John Wiley & Sons, Ltd.

Cited by 24 publications

References 57 publications

Trichinella-induced immunomodulation: Another tale of helminth success

Trichinella-induced immunomodulation: Another tale of helminth success

Preclinical evaluation of a precision medicine approach to DNA vaccination in Type 1 diabetes

microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer

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Vaccination with a co‐expression DNA plasmid containing GAD65 fragment gene and IL‐10 gene induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes

Abstract: Our data suggested that SGAD65190-315 /IL-10 DNA vaccine had protective effects on T1D by upregulating autoantigen-reactive Tregs. Our findings may provide a novel preventive therapy for T1D. Copyright © 2016 John Wiley & Sons, Ltd.

Cited by 24 publications

References 57 publications

Trichinella-induced immunomodulation: Another tale of helminth success

Trichinella-induced immunomodulation: Another tale of helminth success

Preclinical evaluation of a precision medicine approach to DNA vaccination in Type 1 diabetes

microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer

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Vaccination with a co‐expression DNA plasmid containing GAD65 fragment gene and IL‐10 gene induces regulatory CD4⁺ T cells that prevent experimental autoimmune diabetes