Here, we show that AIRE-deficient mice showed an earlier this website development of myelin oligonucleotide glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). To determine the outcome

of ectopic Aire expression, we used a retroviral transduction system to over-express Aire in vitro, in cell lines and in bone marrow (BM). In the cell lines that included those of thymic medullary and dendritic cell origin, ectopically expressed Aire variably promoted expression of TRA including Mog and Ins2 (proII) autoantigens associated, respectively, with the autoimmune diseases multiple sclerosis and type 1 diabetes. BM chimeras generated from BM transduced with a retrovirus encoding Aire displayed elevated levels of Mog and Ins2 expression in thymus and spleen. Following induction of EAE with MOG35–55, transplanted mice displayed significant delay in the onset

of EAE compared with control mice. To our knowledge, this is the first example showing that in vivo ectopic expression of AIRE can modulate TRA expression and alter autoimmune disease development. selleck chemicals llc In humans, deficiency of the autoimmune regulator (AIRE) results in the autosomal recessive disorder, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy otherwise known as autoimmune polyglandular syndrome type 1 1, 2. Studies of Aire−/− mice confirm AIRE as a transcriptional regulator that controls the intra-thymic expression of peripheral tissue-restricted antigens (TRA) implicated in the induction of immunological tolerance 3–5. While the exact number of genes regulated by AIRE is

not known, estimates in mouse and man suggest tuclazepam this may be hundreds to thousands of genes 4, 6–8. Within the thymus, the AIRE protein is expressed predominantly within medullary thymic epithelial cells (mTEC), although expression has also been reported in dendritic cells (DC) 9–11. More recent reports also suggest Aire expression in peripheral cells and tissues 12–15, but its presence and function in these cells still remains an area of debate 9, 16. The generation of AIRE-deficient mice (Aire−/−) has been instrumental in deciphering the role of AIRE in immune tolerance and susceptibility to autoimmune disease. To date, four Aire−/− mouse models have been reported 4, 17–19 and while there is intra- and inter-strain variation, Aire−/− mice develop a range of organ-specific autoimmune diseases that are generally directed towards specific TRA 4, 17, 20, 21.