{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:57:56Z","timestamp":1783393076830,"version":"3.54.6"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:00:00Z","timestamp":1554249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008871","name":"Juvenile Diabetes Research Foundation United States of America","doi-asserted-by":"publisher","award":["5-2010-640"],"award-info":[{"award-number":["5-2010-640"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms20071676","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T11:31:57Z","timestamp":1554377517000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice"],"prefix":"10.3390","volume":"20","author":[{"given":"Julien","family":"Pogu","sequence":"first","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Institut National de la Sant\u00e9 Et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 de Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiria","family":"Tzima","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Biomedical Sciences Research Centre \u201cAlexander Fleming\u201d, Vari, 210 Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Kollias","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Biomedical Sciences Research Centre \u201cAlexander Fleming\u201d, Vari, 210 Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Anegon","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Institut National de la Sant\u00e9 Et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 de Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-8622","authenticated-orcid":false,"given":"Philippe","family":"Blancou","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Institut National de la Sant\u00e9 Et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 de Nantes, 44000 Nantes, France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, 06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Simon","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie, Institut National de la Sant\u00e9 Et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 de Nantes, 44000 Nantes, France"},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur, Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, 06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.advenzreg.2006.01.007","article-title":"Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species","volume":"46","author":"Kobayashi","year":"2006","journal-title":"Adv. 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