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Michaux H, Martens H, Jaïdane H, et al. How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?. Front Immunol. 2015;6:338doi: 10.3389/fimmu.2015.00338.
Michaux, H., Martens, H., Jaïdane, H., Halouani, A., Hober, D., & Geenen, V. (2015). How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?. Frontiers in immunology, 6338. https://doi.org/10.3389/fimmu.2015.00338
Michaux, Hélène, et al. "How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?." Frontiers in immunology vol. 6 (2015): 338. doi: https://doi.org/10.3389/fimmu.2015.00338
Michaux H, Martens H, Jaïdane H, Halouani A, Hober D, Geenen V. How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?. Front Immunol. 2015 Jun 30;6:338. doi: 10.3389/fimmu.2015.00338. eCollection 2015. PMID: 26175734; PMCID: PMC4485212.
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Front Immunol. 2015 Jun 30;6:338. doi: 10.3389/fimmu.2015.00338. eCollection 2015.

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

Frontiers in immunology

Hélène Michaux, Henri Martens, Hela Jaïdane, Aymen Halouani, Didier Hober, Vincent Geenen

Affiliations

  1. Department of Biomedical and Preclinical Sciences, GIGA-I?3 Center of Immunoendocrinology, GIGA Research Institute, University of Liege , Liege , Belgium.
  2. Laboratory of Virology LR99ES27, School of Pharmacy, University of Monastir , Monastir , Tunisia ; Faculty of Sciences of Tunis, University of Tunis El Manar , Tunis , Tunisia.
  3. Laboratory of Virology EA3610, Centre Hospitalier Régional Universitaire de Lille, University of Lille 2 , Lille , France.

PMID: 26175734 PMCID: PMC4485212 DOI: 10.3389/fimmu.2015.00338

Abstract

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.

Keywords: coxsackievirus; enterovirus; insulin family; insulin-like growth factor 2; self-tolerance; thymus; type 1 diabetes

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