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Publication : Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity.

First Author  Gavanescu I Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  11 Pages  4583-7
PubMed ID  17360567 Mgi Jnum  J:119475
Mgi Id  MGI:3702256 Doi  10.1073/pnas.0700259104
Citation  Gavanescu I, et al. (2007) Loss of Aire-dependent thymic expression of a peripheral tissue antigen renders it a target of autoimmunity. Proc Natl Acad Sci U S A 104(11):4583-7
abstractText  Both humans and mice with a mutation in the autoimmune regulator (aire) gene develop multiorgan autoimmune disease. Aire was shown to exert its critical function in medullary epithelial cells of the thymus by promoting ectopic expression of peripheral tissue antigens. It was hypothesized that the widespread autoimmunity of Aire-deficient individuals reflects a lack of tolerance induction to the repertoire of peripheral tissue antigens expressed in the thymus of normal individuals. Here, we substantiate this hypothesis by identifying Mucin 6 as a stomach-specific antigen targeted by autoantibodies in gastritis-prone mice lacking thymic expression of aire and demonstrate that transcription of the Mucin 6 gene in thymic medullary epithelial cells is indeed Aire-dependent.
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