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

Centre de Recherche en Transplantation et Immunologie, Institut National de la Santé Et de la Recherche Médicale (INSERM), Université de Nantes, 44000 Nantes, France
Institute of Immunology, Biomedical Sciences Research Centre “Alexander Fleming”, Vari, 210 Attica, Greece
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;
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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