Reference : How does thymus infection by coxsackievirus contribute to the pathogenesis of type 1 ...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
Human health sciences : Endocrinology, metabolism & nutrition
How does thymus infection by coxsackievirus contribute to the pathogenesis of type 1 diabetes?
Michaux, Hélène [Université de Liège > > Centre d'immunologie >]
Martens, Henri mailto [Université de Liège > > Centre d'immunologie >]
Jaïdane, Hela mailto [University of Tunis El Mansar > Faculty of Sciences > > >]
Halouani, Aymen mailto []
Hober, Didier mailto [University of Lille 2 and CHRU Lille > Laboratory of Virology EA3610 > > >]
Geenen, Vincent mailto [Université de Liège > > Centre d'immunologie >]
Frontiers in Immunology
Article 338
[en] Enterovirus ; Coxsackievirus ; Thymus ; Self-tolerance ; Type 1 diabetes ; Insulin family ; Insulin-like growth factor 2
[en] Through synthesis and presentation of neuroendocrine self-antigens by major histocom- patibility 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.
Giga-Infection, Immunity and Inflammation / Immunoendocrinology
Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture (Communauté française de Belgique) - FRIA ; Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Union Européenne = European Union - UE = EU
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