Danger-free autoimmune disease in Aire-deficient mice

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 ..