Endocrine Abstracts

The autoimmune regulator protein (AIRE) is a critical component of thymic education which leads to immune tolerance. Its recent detection in extrathymic tissues has prompted inquiry into potential roles for this protein beyond the thymus. We have reported detecting AIRE in circulating CD34+ fibrocytes, monocyte progenitor cells that are involved in tissue reactivity and remodeling. These fibrocytes have been detected in orbital connective tissue from individuals with thyroid associated ophthalmopathy and in thyroid tissue from patients with Graves’ disease. Further, fibrocytes express functional TSH receptor, thyroglobulin, sodium iodide symporter, and thyroperoxidase. We therefore interrogated these cells for the expression of AIRE and found that both full length and truncated forms of the protein could be detected. When AIRE expression was knocked down with specific targeting SIRNAs, levels of all four thyroid associated proteins were substantially reduced. Analysis of fibrocytes from an individual with APS1 disclosed reduced levels of these proteins as well. These findings suggest that AIRE may play an important role in the expression of thyroid self-antigens outside the thyroid. It is possible that AIRE dependent expression of thyroid antigens by fibrocytes may be involved in the manifestations of Graves’ disease such as thyroid associated ophthalmopathy.