[Apoptosis in Hashimoto's thyroiditis]

It has been suggested that apoptosis plays a pivotal role in the pathogenesis of autoimmune diseases. In Hashimoto's thyroiditis which is a typical organ-specific autoimmune disease, Fas-FasL-mediated apoptosis has been demonstrated as the mechanism of follicular epithelial cell death in which Fas is expressed by IL-1 beta stimulation of FasL is constitutively expressed on follicular epithelial cells. The processes involved in this finding and some questions concerning epithelial cell death are presented. The thyroid tissue of Hashimoto's thyroiditis was examined for DNA fragmentation of follicular epithelial cells by the TUNEL method. DNA fragmentation was observed more frequently on thyroid follicles in the area adjacent to lymphoid cell follicles than on those in the central area. Electron microscopic study supported the results of TUNEL study. Immunohistochemical study on Fas and FasL expression on follicular epithelial cells of various thyroid diseases showed that Fas and FasL were strongly expressed on follicular epithelial cells in Hashimoto's thyroiditis and thyroid cancer. Epithelial cells of patients with Graves' disease and adenomatous goiter, however, were scarcely stained. Fas and FasL expression on follicular epithelial cells were well correlated. In vitro study on follicular epithelial cells clarified that FasL was constitutively expressed on epithelial cells not only in Hashimoto's thyroiditis but also in nontoxic goiter. Fas expression was induced by IL-1 beta stimulation. IL-1 beta stimulation also brought about apoptosis of epithelial cells and epithelial cells killed Fas-positive target cells. Therefore, it was concluded that FasL expressed constitutively on follicular epithelial cells interacts with Fas on epithelial cells expressed by IL-1 beta stimulation to induce apoptosis of epithelial cells.