Danger-free autoimmune disease in Aire-deficient mice. Gray, D. H. D. et al. Proc. Natl Acad. Sci. USA 104, 18193–18198 (2007)
Autoimmune regulator (AIRE) deficiency in mice results in the development of spontaneous, multiorgan autoimmunity, owing to a defect in the removal of autoreactive T cells. It has been proposed that stimulation of the innate immune system by environmental factors is required to activate these autoreactive T cells in the periphery (the danger theory of immune tolerance). Here, Gray et al. show that various compounds that are known to stimulate the innate immune system did not modulate the disease symptoms in Aire−/− mice on either the C57BL/6 or NOD (non-obese diabetic) background. A defect in Toll-like receptor signalling did not prevent the induction of autoimmunity in Aire−/− NOD mice. Furthermore, by using germ-free mice the authors showed that autoimmunity develops in the absence of microbial colonization in Aire−/− NOD mice. So, this study indicates that autoimmune disease in AIRE-deficient mice can develop without environmental stimulation.
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