Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pogu, Julien, Tzima, Sotiria, Kollias, Georges, Anegon, Ignacio, Blancou, Philippe, Simon, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480274/
https://www.ncbi.nlm.nih.gov/pubmed/30987262
http://dx.doi.org/10.3390/ijms20071676
_version_ 1783413538773008384
author Pogu, Julien
Tzima, Sotiria
Kollias, Georges
Anegon, Ignacio
Blancou, Philippe
Simon, Thomas
author_facet Pogu, Julien
Tzima, Sotiria
Kollias, Georges
Anegon, Ignacio
Blancou, Philippe
Simon, Thomas
author_sort Pogu, Julien
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6480274
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64802742019-04-29 Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice Pogu, Julien Tzima, Sotiria Kollias, Georges Anegon, Ignacio Blancou, Philippe Simon, Thomas Int J Mol Sci Article 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. MDPI 2019-04-03 /pmc/articles/PMC6480274/ /pubmed/30987262 http://dx.doi.org/10.3390/ijms20071676 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pogu, Julien
Tzima, Sotiria
Kollias, Georges
Anegon, Ignacio
Blancou, Philippe
Simon, Thomas
Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
title Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
title_full Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
title_fullStr Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
title_full_unstemmed Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
title_short Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice
title_sort genetic restoration of heme oxygenase-1 expression protects from type 1 diabetes in nod mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480274/
https://www.ncbi.nlm.nih.gov/pubmed/30987262
http://dx.doi.org/10.3390/ijms20071676
work_keys_str_mv AT pogujulien geneticrestorationofhemeoxygenase1expressionprotectsfromtype1diabetesinnodmice
AT tzimasotiria geneticrestorationofhemeoxygenase1expressionprotectsfromtype1diabetesinnodmice
AT kolliasgeorges geneticrestorationofhemeoxygenase1expressionprotectsfromtype1diabetesinnodmice
AT anegonignacio geneticrestorationofhemeoxygenase1expressionprotectsfromtype1diabetesinnodmice
AT blancouphilippe geneticrestorationofhemeoxygenase1expressionprotectsfromtype1diabetesinnodmice
AT simonthomas geneticrestorationofhemeoxygenase1expressionprotectsfromtype1diabetesinnodmice