Diabetes: the virus that causes intolerance to insulin
While an increasing number of studies, mainly epidemiological, seem to show that coxsackieviruses (CVs) play a role in the appearance of autoimmune type 1 diabetes, the mechanisms of action of these viruses remain vague. As part of the European FP6 Eurothymaide project, Vincent Geenen and his team, in close collaboration with Lille’s CHRU hospital (Didier Hober), the Centre d’Immunologie de Marseille-Luminy (Philippe Naquet) and the University of Tunis, have however discovered that infection of the thymus by the diabetogenic CVB4 virus leads to a decrease in the transcription of the IGF2 gene (Insulin-like Growth Factor 2). “And yet, this factor plays a major role in establishing the immune system’s tolerance to insulin”, Vincent Geenen explains. In short, the CVB4 virus infects the thymus epithelial cells, reproduces therein and decreases the production of IGF2 by these cells. It would appear that this drastic reduction in thymic IGF2 makes the body immune system intolerant to insulin, the hormone secreted by the pancreas whose deficiency causes autoimmune type 1 diabetes. The results of this study have just been published in the Journal of Virology (1). But Vincent Geenen’s team is now focusing on the development of a new type of vaccine that would reprogram immune tolerance to the endocrine pancreas beta cells and thus contribute to both the prevention and cure of T1D. Double control against autoimmunity“The thymus, or rather its dysfunction, may play a major role in the appearance of this disease because it’s here that the immune system is educated. It learns to recognise major hormone families such as insulin”, explains the professor. In other words, the thymus is the safeguard of the adaptive immune system. Appearing in cartilaginous fishes (sharks and rays) about 450 million years ago, the adaptive immune system allows us to react specifically (contrary to the innate immune system which is non-specific) against any pathogen that enters our body. The thymus made its appearance at almost the same time and it is here that the T lymphocytes differentiate and reach maturity (2). (1) Jaïdane H, Caloone D, Lobert PE, Sane F, Dardenne O, Naquet P, Gharbi J, Aouni M, Geenen V, Hober D. Persistent infection of thymic epithelial cells with coxsackievirus B4 results in decreased expression of type 2 insulin-like growth factor. J Virol. 2012 Oct;86(20):11151-62. Epub 2012 Aug 1. (2) Geenen V. Presentation of neuroendocrine self in the thymus: a necessity for integrated evolution of the immune and neuroendocrine systems. Ann NY Acad Sci. 2012;1261:42-48. |
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