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How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?

Through synthesis and presentation of neuroendocrine self-antigens by major histocompatibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor-2 (IGF-2) is the dominant gene/polyp...

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Autores principales: Michaux, Hélène, Martens, Henri, Jaïdane, Hela, Halouani, Aymen, Hober, Didier, Geenen, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485212/
https://www.ncbi.nlm.nih.gov/pubmed/26175734
http://dx.doi.org/10.3389/fimmu.2015.00338
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author Michaux, Hélène
Martens, Henri
Jaïdane, Hela
Halouani, Aymen
Hober, Didier
Geenen, Vincent
author_facet Michaux, Hélène
Martens, Henri
Jaïdane, Hela
Halouani, Aymen
Hober, Didier
Geenen, Vincent
author_sort Michaux, Hélène
collection PubMed
description Through synthesis and presentation of neuroendocrine self-antigens by major histocompatibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor-2 (IGF-2) is the dominant gene/polypeptide of the insulin family that is expressed in TECs from different animal species and humans. Igf2 transcription is defective in the thymus of diabetes-prone bio-breeding rats, and tolerance to insulin is severely decreased in Igf2(−/−) mice. For more than 15 years now, our group is investigating the hypothesis that, besides a pancreotropic action, infection by coxsackievirus B4 (CV-B4) could implicate the thymus as well, and interfere with the intrathymic programing of central tolerance to the insulin family and secondarily to insulin-secreting islet β cells. In this perspective, we have demonstrated that a productive infection of the thymus occurs after oral CV-B4 inoculation of mice. Moreover, our most recent data have demonstrated that CV-B4 infection of a murine medullary (m) TEC line induces a significant decrease in Igf2 expression and IGF-2 production. In these conditions, Igf1 expression was much less affected by CV-B4 infection, while Ins2 transcription was not detected in this cell line. Through the inhibition of Igf2 expression in TECs, CV-B4 infection could lead to a breakdown of central immune tolerance to the insulin family and promote an autoimmune response against insulin-secreting islet β cells. Our major research objective now is to understand the molecular mechanisms by which CV-B4 infection of TECs leads to a major decrease in Igf2 expression in these cells.
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spelling pubmed-44852122015-07-14 How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes? Michaux, Hélène Martens, Henri Jaïdane, Hela Halouani, Aymen Hober, Didier Geenen, Vincent Front Immunol Immunology Through synthesis and presentation of neuroendocrine self-antigens by major histocompatibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor-2 (IGF-2) is the dominant gene/polypeptide of the insulin family that is expressed in TECs from different animal species and humans. Igf2 transcription is defective in the thymus of diabetes-prone bio-breeding rats, and tolerance to insulin is severely decreased in Igf2(−/−) mice. For more than 15 years now, our group is investigating the hypothesis that, besides a pancreotropic action, infection by coxsackievirus B4 (CV-B4) could implicate the thymus as well, and interfere with the intrathymic programing of central tolerance to the insulin family and secondarily to insulin-secreting islet β cells. In this perspective, we have demonstrated that a productive infection of the thymus occurs after oral CV-B4 inoculation of mice. Moreover, our most recent data have demonstrated that CV-B4 infection of a murine medullary (m) TEC line induces a significant decrease in Igf2 expression and IGF-2 production. In these conditions, Igf1 expression was much less affected by CV-B4 infection, while Ins2 transcription was not detected in this cell line. Through the inhibition of Igf2 expression in TECs, CV-B4 infection could lead to a breakdown of central immune tolerance to the insulin family and promote an autoimmune response against insulin-secreting islet β cells. Our major research objective now is to understand the molecular mechanisms by which CV-B4 infection of TECs leads to a major decrease in Igf2 expression in these cells. Frontiers Media S.A. 2015-06-30 /pmc/articles/PMC4485212/ /pubmed/26175734 http://dx.doi.org/10.3389/fimmu.2015.00338 Text en Copyright © 2015 Michaux, Martens, Jaïdane, Halouani, Hober and Geenen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Michaux, Hélène
Martens, Henri
Jaïdane, Hela
Halouani, Aymen
Hober, Didier
Geenen, Vincent
How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?
title How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?
title_full How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?
title_fullStr How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?
title_full_unstemmed How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?
title_short How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?
title_sort how does thymus infection by coxsackievirus contribute to the pathogenesis of type 1 diabetes?
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485212/
https://www.ncbi.nlm.nih.gov/pubmed/26175734
http://dx.doi.org/10.3389/fimmu.2015.00338
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