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

Journal article

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.

Authors: Gavanescu, I; Kessler, B; Ploegh, H; Benoist, C; Mathis, D

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 104
• Issue: 11
• Pages: 4583-4587
• Publication date: 2007-03-01
• DOI: 10.1073/pnas.0700259104
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Amino Acid Sequence; Mutation; Humans; Mucins; Autoimmune Diseases; Bone Marrow Cells; Gene Expression Regulation; Autoimmunity; Animals; Epithelial Cells; Mice; Mucin-6; Mice, Inbred BALB C; Molecular Sequence Data; Thymus Gland; Transcription Factors