NDLI: Danger-free autoimmune disease in Aire-deficient mice

Content Provider	PubMed Central
Author	Gray, Daniel H. D. Irina, Gavanescu Benoist, Christophe Mathis, Diane
Copyright Year	2007
Abstract	The danger theory of immune tolerance asserts that environmental factors hold primacy over lymphocyte autoreactivity in initiating autoimmune disease. We sought to test this contention using the Aire-deficient mouse model of the human disease, autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy, a multiorgan autoimmune disorder rooted in a lesion in thymic tolerance. Compound screens stimulating a broad range of innate immune system pathways failed to show any modulation of disease characteristics in Aire −/− mice on either the C57BL/6 or NOD genetic backgrounds. Furthermore, deficiency in the Toll-like receptor adaptor Myd88 increased the lifespan of NOD.aire −/− mice but did not prevent the initiation of autoimmunity. Finally, germ-free NOD.aire −/− mice exhibited autoimmunity in all organs normally targeted in this model, indicating that microbial conditioning is not required for activation of autoreactive T cells relevant to this disease. Together, these data suggest that the stochastic genesis of dangerous T cell clones can initiate autoimmune disease without the need for environmental stimulation, underlining the importance of Aire-dependent thymic deletion.
Related Links	http://dx.doi.org/10.1073/pnas.0709160104
Ending Page	18198
Page Count	6
Starting Page	18193
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	46
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-11-13
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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