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Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus

Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), t...

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Autores principales: Halouani, Aymen, Michaux, Hélène, Jmii, Habib, Trussart, Charlotte, Chahbi, Ahlem, Martens, Henri, Renard, Chantal, Aouni, Mahjoub, Hober, Didier, Geenen, Vincent, Jaïdane, Hela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303261/
https://www.ncbi.nlm.nih.gov/pubmed/34361972
http://dx.doi.org/10.3390/microorganisms9071537
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author Halouani, Aymen
Michaux, Hélène
Jmii, Habib
Trussart, Charlotte
Chahbi, Ahlem
Martens, Henri
Renard, Chantal
Aouni, Mahjoub
Hober, Didier
Geenen, Vincent
Jaïdane, Hela
author_facet Halouani, Aymen
Michaux, Hélène
Jmii, Habib
Trussart, Charlotte
Chahbi, Ahlem
Martens, Henri
Renard, Chantal
Aouni, Mahjoub
Hober, Didier
Geenen, Vincent
Jaïdane, Hela
author_sort Halouani, Aymen
collection PubMed
description Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), thus preventing autoimmunity. Thymus infection by Coxsackievirus B (CV-B) during fetal life is supposed to disturb thymic functions and, hence, to be an inducing or accelerating factor in the genesis of autoimmunity. To further investigate this hypothesis, in our current study, we analyzed thymic expression of autoantigens, at the transcriptional and protein level, following in utero infection by CV-B4. mRNA expression levels of Igf2 and Myo7, major autoantigens of pancreas and heart, respectively, were analyzed in whole thymus and in enriched TECs together along with both transcription factors, Aire and Fezf2, involved in autoantigens expression in the thymus. Results show that in utero infection by CV-B4 induces a significant decrease in Igf2 and Myo7 expression at both mRNA and protein level in whole thymus and in enriched TECs as well. Moreover, a correlation between viral load and autoantigens expression can be observed in the whole thymus, indicating a direct effect of in utero infection by CV-B4 on autoantigens expression. Together, these results indicate that an in utero infection of the thymus by CV-B4 may interfere with self-tolerance establishment in TECs by decreasing autoantigen expression at both mRNA and protein level and thereby increase the risk of autoimmunity onset.
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spelling pubmed-83032612021-07-25 Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus Halouani, Aymen Michaux, Hélène Jmii, Habib Trussart, Charlotte Chahbi, Ahlem Martens, Henri Renard, Chantal Aouni, Mahjoub Hober, Didier Geenen, Vincent Jaïdane, Hela Microorganisms Article Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), thus preventing autoimmunity. Thymus infection by Coxsackievirus B (CV-B) during fetal life is supposed to disturb thymic functions and, hence, to be an inducing or accelerating factor in the genesis of autoimmunity. To further investigate this hypothesis, in our current study, we analyzed thymic expression of autoantigens, at the transcriptional and protein level, following in utero infection by CV-B4. mRNA expression levels of Igf2 and Myo7, major autoantigens of pancreas and heart, respectively, were analyzed in whole thymus and in enriched TECs together along with both transcription factors, Aire and Fezf2, involved in autoantigens expression in the thymus. Results show that in utero infection by CV-B4 induces a significant decrease in Igf2 and Myo7 expression at both mRNA and protein level in whole thymus and in enriched TECs as well. Moreover, a correlation between viral load and autoantigens expression can be observed in the whole thymus, indicating a direct effect of in utero infection by CV-B4 on autoantigens expression. Together, these results indicate that an in utero infection of the thymus by CV-B4 may interfere with self-tolerance establishment in TECs by decreasing autoantigen expression at both mRNA and protein level and thereby increase the risk of autoimmunity onset. MDPI 2021-07-19 /pmc/articles/PMC8303261/ /pubmed/34361972 http://dx.doi.org/10.3390/microorganisms9071537 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Halouani, Aymen
Michaux, Hélène
Jmii, Habib
Trussart, Charlotte
Chahbi, Ahlem
Martens, Henri
Renard, Chantal
Aouni, Mahjoub
Hober, Didier
Geenen, Vincent
Jaïdane, Hela
Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus
title Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus
title_full Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus
title_fullStr Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus
title_full_unstemmed Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus
title_short Coxsackievirus B4 Transplacental Infection Severely Disturbs Central Tolerogenic Mechanisms in the Fetal Thymus
title_sort coxsackievirus b4 transplacental infection severely disturbs central tolerogenic mechanisms in the fetal thymus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303261/
https://www.ncbi.nlm.nih.gov/pubmed/34361972
http://dx.doi.org/10.3390/microorganisms9071537
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