The intrathymic expression of insulin-related genes: implications for pathophysiology and prevention of Type 1 diabetes.
Recent experimental work has challenged and shattered the old concept of a sequestration of pancreatic islet antigens from developing T-cells within the thymic environment. There is now compelling evidence that the central immunological tolerance of the whole insulin family may be induced during the process of T-cell ontogeny in the thymus. Transcripts of insulin-like growth factor II (IGF-II), IGF-I and insulin genes have been characterized in human, rat and mouse thymuses. At the peptide level, IGF-II was shown to be the dominant polypeptide of the insulin family in the thymus from different species. Data are presented which support a dual role of thymic IGF-II both in T-cell development as well as in T-cell negative selection. Using animal models of autoimmune diabetes, current research is investigating the hypothesis that a defect of thymic T-cell education to the insulin family is implicated in the pathophysiology of human Type 1 diabetes. An efficient and secure prevention of Type 1 diabetes could be designed on the basis of the strong natural tolerogenic properties of the thymus.
Geenen
V
V
Department of Medicine and Institute of Pathology, University of Liège, Belgium.
Lefèbvre
P J
PJ
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D015870:Gene Expression / Q000235:genetics; D005796:Genes / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000502:physiology; D013950:Thymus Gland / Q000737:chemistry / Q000378:metabolism*
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II