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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 2017 (9)

Title and authors Publication Year
Microbiota control immune regulation in humanized mice
Elke Gulden, Nalini Vudattu, songyan deng, Paula Preston-Hurlburt, Mark Mamula, J C Reed, Sindu Mohandas, Betsy Herold, Richard Torres, Silvio Vieira, Bentley Lim, Jose D.Herazo-Maya, Martin Kriegel, Andrew Goodman, Chris Cotsapas, Kevan Herold
JCI Insight 2017
Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development
H Yu, N Gagliani, H Ishigame, S Huber, S Zhu, E Esplugues, KC Herold, L Wen, RA Flavell
Proceedings of the National Academy of Sciences 2017
Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches
AR Basson, M Lam, F Cominelli
Gastroenterology Clinics of North America 2017
Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice
AL Posgai, CH Wasserfall, KC Kwon, H Daniell, DA Schatz, MA Atkinson
Scientific Reports 2017
Early-Life Nutritional Factors and Mucosal Immunity in the Development of Autoimmune Diabetes
L Xiao, B Land, WR van de Worp, B Stahl, G Folkerts, J Garssen
Frontiers in immunology 2017
Sustainable therapies by engineered bacteria
B Álvarez, LÁ Fernández
Microbial Biotechnology 2017
Synthetic Biology and the Gut Microbiome
J Dou, MR Bennett
Biotechnology Journal 2017
Small molecule signaling, regulation, and potential applications in cellular therapeutics: Small molecule signaling, regulation, and potential applications in cellular therapeutics
MP McNerney, MP Styczynski
Wiley interdisciplinary reviews. Systems biology and medicine 2017
Engineering Diagnostic and Therapeutic Gut Bacteria
BP Landry, JJ Tabor, RA Britton, PD Cani
Microbiology spectrum 2017

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