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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.

Original publication

DOI

10.1073/pnas.0700259104

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

13/03/2007

Volume

104

Pages

4583 - 4587

Keywords

Amino Acid Sequence, Animals, Autoimmune Diseases, Autoimmunity, Bone Marrow Cells, Epithelial Cells, Gene Expression Regulation, Humans, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mucin-6, Mucins, Mutation, Thymus Gland, Transcription Factors