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Citations to this article

Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice
Tatiana Takiishi, … , Conny Gysemans, Chantal Mathieu
Tatiana Takiishi, … , Conny Gysemans, Chantal Mathieu
Published April 9, 2012
Citation Information: J Clin Invest. 2012;122(5):1717-1725. https://doi.org/10.1172/JCI60530.
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Research Article Autoimmunity Article has an altmetric score of 35

Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice

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Abstract

Current interventions for arresting autoimmune diabetes have yet to strike the balance between sufficient efficacy, minimal side effects, and lack of generalized immunosuppression. Introduction of antigen via the gut represents an appealing method for induction of antigen-specific tolerance. Here, we developed a strategy for tolerance restoration using mucosal delivery in mice of biologically contained Lactococcus lactis genetically modified to secrete the whole proinsulin autoantigen along with the immunomodulatory cytokine IL-10. We show that combination therapy with low-dose systemic anti-CD3 stably reverted diabetes in NOD mice and increased frequencies of local Tregs, which not only accumulated in the pancreatic islets, but also suppressed immune response in an autoantigen-specific way. Cured mice remained responsive to disease-unrelated antigens, which argues against excessive immunosuppression. Application of this therapeutic tool achieved gut mucosal delivery of a diabetes-relevant autoantigen and a biologically active immunomodulatory cytokine, IL-10, and, when combined with a low dose of systemic anti-CD3, was well tolerated and induced autoantigen-specific long-term tolerance, allowing reversal of established autoimmune diabetes. Therefore, we believe this method could be an effective treatment strategy for type 1 diabetes in humans.

Authors

Tatiana Takiishi, Hannelie Korf, Tom L. Van Belle, Sofie Robert, Fabio A. Grieco, Silvia Caluwaerts, Letizia Galleri, Isabella Spagnuolo, Lothar Steidler, Karolien Van Huynegem, Pieter Demetter, Clive Wasserfall, Mark A. Atkinson, Francesco Dotta, Pieter Rottiers, Conny Gysemans, Chantal Mathieu

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 2 6 6 7 9 15 6 3 9 8 6 6 9 5 97
Citation information
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Citations to this article in year 2022 (7)

Title and authors Publication Year
Anti-Diabetic Potential of Chlorella Pyrenoidosa-Based Mixture and its Regulation of Gut Microbiota.
Xiong W, Chen J, He J, Xiao M, He X, Liu B, Zeng F
Plant Foods for Human Nutrition 2022
Microbiota in health and diseases
Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, Zhu D, Koya JB, Wei L, Li J, Chen ZS
Signal Transduction and Targeted Therapy 2022
Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target
Zhang T, Gao G, Sakandar HA, Kwok LY, Sun Z
Frontiers in Nutrition 2022
Effects of broad-spectrum antibiotics on the colonisation of probiotic yeast Saccharomyces boulardii in the murine gastrointestinal tract
Hedin KA, Rees VE, Zhang H, Kruse V, Vazquez-Uribe R, Sommer MO
Scientific Reports 2022
From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes
den Hollander NH, Roep BO
Frontiers in Medicine 2022
Biotechnological Applications of Probiotics: A Multifarious Weapon to Disease and Metabolic Abnormality
Singh RP, Shadan A, Ma Y
Probiotics and Antimicrobial Proteins 2022
Postbiotics and Kidney Disease
Favero C, Giordano L, Mihaila SM, Masereeuw R, Ortiz A, Sanchez-Niño MD
Toxins 2022

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