Neuroendocrine immuno-ontogeny of the pathogenesis of autoimmune disease in the nonobese diabetic (NOD) mouse.
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which insulin-producing beta cells of the pancreatic islets of Langerhans are destroyed. The nonobese diabetic (NOD) mouse is one of the rare spontaneous models that enable the study of prediabetic pancreatic events. The etiology of the autoimmune attack in human and animal T1D is still unknown, but genetic and environmental factors are involved in both cases. Although several autoantigens have been identified and defective immune-system regulation is implicated, this information does not satisfactorily explain the generally accepted beta-cell specificity of the disease or how so many and diverse environmental factors intervene in its pathogenesis. Based on data obtained from evaluating glucose homeostasis in a variety of situations, particularly stress and cytokine administration, in young prediabetic NOD mice, the author hypothesizes that the islet of Langerhans is a major actor, and its altered regulation through environmentally induced insulin resistance might reveal latent T1D. It is also postulated that T1D pathogenesis might be linked to abnormal pancreas development, probably due to disturbances of glutamic acid decarboxylase (GAD)+ innervation phagocytosis by defective macrophages during the early postnatal period. Also discussed is the role of defective presentation of pancreatic hormones and GAD in the thymus, and its potential repercussion on T-cell tolerance. Observations have demonstrated that the diabetogenic process in the NOD mouse is extremely complex, involving neuroendocrine immune interaction from fetal life onward.
Homo-Delarche
Françoise
F
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université Paris 7/D.Diderot, Paris, France.
D000818:Animals; D001324:Autoantigens / Q000032:analysis; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009490:Neurosecretory Systems / Q000276:immunology*
D001324:Autoantigens