Loss of Aire-dependent Thymic Expression of a Peripheral Tissue Antigen Renders It a Target of Autoimmunity

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Mar 16

PMID 17360567

Citations 44

Authors

Irina Gavanescu

Benedikt Kessler

Hidde Ploegh

Christophe Benoist

Diane Mathis

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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