| First Author | Gray DH | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 46 | Pages | 18193-8 |
| PubMed ID | 17991771 | Mgi Jnum | J:127308 |
| Mgi Id | MGI:3763557 | Doi | 10.1073/pnas.0709160104 |
| Citation | Gray DH, et al. (2007) Danger-free autoimmune disease in Aire-deficient mice. Proc Natl Acad Sci U S A 104(46):18193-8 |
| abstractText | 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. |
