O papel modulador do gene AIRE - capes

MANUSCRITOdominated the scenario in explaining self-non-self discrimination (Alferink etal., 1999; Walkerand Abbas 2002).Promiscuous gene expression in the thymus is causing a reversal in thescope of central tolerance understanding, allowing for an unorthodoxconception of the possible mechanisms of self-non-self discrimination(Kyewsky et al., 2002, Gallegos and Bevan, 2006; Magalhães et al., 2006;Sousa Cardoso et al., 2006).The main implication of this heterogeneous gene expression in thethymus is associated with the maintenance of the immunologicalhomeostasis in the body, controlling the pathogenic autoimmune reactions.Evidence for this phenomenon was obtained using the reversetranscription-PCR (RT-PCR) method, which was biased towards antigens inautoimmune reactions, such as insulin, acetylcholine receptor or myelinbasic protein. Today it is recognized that rather than selective, the set ofexpressed genes is as broad as possible, and involves up to 5-10% of the allknown mouse genes (Derbinski et al., 2001; Gotter et al., 2004; Kyewski andDerbinski, 2004).The extent of self-representation of most parenchymal tissues andorgans is guaranteed by PGE in the thymus, a phenomenon exhibited bymTECs. Accordingly, the complexity of PGE increases in ascending order,from cortical thymic epithelial cells (cTECs) to immature mTECs to matureCD80+ mTECs. These different gene pools are not complementary butadditive, that is, there is no apparent association between the respectivemolecular/biological function of the genes in parenchymal organs. Thesignificance of PGE in the thymus is associated with central tolerance of T205