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

Julien Pogu 1 Sotiria Tzima 2 Georges Kollias 2 Ignacio Anegon 3 Philippe Blancou 1, 4 Thomas Simon 1, 4, *
* Corresponding author
1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 Institute of Immunology [Attica, Greece]
3 Team 2 - U1064 Inserm - CRTI - Genetic and Cellular Engineering in Immunology and Regenerative Medicine
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
4 IPMC - Institut de pharmacologie moléculaire et cellulaire
Abstract : 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.
Keywords : ANTIGEN presenting cell tolerance Tet-ON system antigen presentation
Document type :
Journal articles
Complete list of metadatas

Cited literature [39 references]  Display  Hide  Download
https://www.hal.inserm.fr/inserm-02145830
Contributor : Ana Paula Dutra Azevedo <>
Submitted on : Monday, June 3, 2019 - 1:13:41 PM
Last modification on : Thursday, January 16, 2020 - 10:20:07 AM

File

2019Genetic_ijms-20-01676-v2 (...
Publisher files allowed on an open archive

Identifiers

Collections

CNRS | UNICE | UNIV-COTEDAZUR | UNIV-NANTES | CRTI

Citation

Julien Pogu, Sotiria Tzima, Georges Kollias, Ignacio Anegon, Philippe Blancou, et al.. Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice. International Journal of Molecular Sciences, MDPI, 2019, 20 (7), pp.1676. ⟨10.3390/ijms20071676⟩. ⟨inserm-02145830⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

61

Files downloads

94

Contact

Informations

CCSD