The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus

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Abstract
It has been more than 20 years since the AIRE gene was discovered. The mutations in the AIRE gene cause a rare and life-threatening autoimmune disease with severe manifestations against a variety of organs. Since the identification of the AIRE gene in 1997, more than two decades of investigations have revealed key insights into the role of AIRE and its mode of action. These studies have shown that AIRE uniquely induces the expression of thousands of tissue-restricted self-antigens in the thymus. These self-antigens are presented to developing T cells, resulting in the deletion of the self-reactive T cells and the generation of regulatory T cells. Thus, AIRE is a master guardian in establishing and maintaining central immune tolerance.

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