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Open AccessArticle

Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice

1
Centre de Recherche en Transplantation et Immunologie, Institut National de la Santé Et de la Recherche Médicale (INSERM), Université de Nantes, 44000 Nantes, France
2
Institute of Immunology, Biomedical Sciences Research Centre “Alexander Fleming”, Vari, 210 Attica, Greece
3
Université Côte d’Azur, Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie Moléculaire et Cellulaire, 06560 Valbonne, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1676; https://doi.org/10.3390/ijms20071676
Received: 5 March 2019 / Revised: 28 March 2019 / Accepted: 29 March 2019 / Published: 3 April 2019
(This article belongs to the Special Issue Protective and Detrimental Role of Heme Oxygenase-1)
Antigen-presenting cells (APCs) including dendritic cells (DCs) play a critical role in the development of autoimmune diseases by presenting self-antigen to T-cells. Different signals modulate the ability of APCs to activate or tolerize autoreactive T-cells. Since the expression of heme oxygenase-1 (HO-1) by APCs has been associated with the tolerization of autoreactive T-cells, we hypothesized that HO-1 expression might be altered in APCs from autoimmune-prone non-obese diabetic (NOD) mice. We found that, compared to control mice, NOD mice exhibited a lower percentage of HO-1-expressing cells among the splenic DCs, suggesting an impairment of their tolerogenic functions. To investigate whether restored expression of HO-1 in APCs could alter the development of diabetes in NOD mice, we generated a transgenic mouse strain in which HO-1 expression can be specifically induced in DCs using a tetracycline-controlled transcriptional activation system. Mice in which HO-1 expression was induced in DCs exhibited a lower Type 1 Diabetes (T1D) incidence and a reduced insulitis compared to non-induced mice. Upregulation of HO-1 in DCs also prevented further increase of glycemia in recently diabetic NOD mice. Altogether, our data demonstrated the potential of induction of HO-1 expression in DCs as a preventative treatment, and potential as a curative approach for T1D. View Full-Text
Keywords: ANTIGEN presenting cell; tolerance; Tet-ON system; antigen presentation ANTIGEN presenting cell; tolerance; Tet-ON system; antigen presentation
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Pogu, J.; Tzima, S.; Kollias, G.; Anegon, I.; Blancou, P.; Simon, T. Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice. Int. J. Mol. Sci. 2019, 20, 1676.

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