 |
Journal articles
Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
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.
Cited literature [39 references]
https://www.hal.inserm.fr/inserm-02145830
Contributor : Sylvie Le Bihan Connect in order to contact the contributor
Submitted on : Monday, June 3, 2019 - 1:13:41 PM
Last modification on : Tuesday, January 4, 2022 - 6:36:05 AM
Contributor : Sylvie Le Bihan Connect in order to contact the contributor
Submitted on : Monday, June 3, 2019 - 1:13:41 PM
Last modification on : Tuesday, January 4, 2022 - 6:36:05 AM
File
2019Genetic_ijms-20-01676-v2 (...
Publisher files allowed on an open archive