POTENTIAL INVOLVEMENT OF FAS AND ITS LIGAND IN THE PATHOGENESIS OF HASHIMOTOS-THYROIDITIS

The mechanisms responsible for thyrocyte destruction in Hashimoto's th yroiditis (HT) are poorly understood. Thyrocytes from HT glands, but n ot from nonautoimmune thyroids, expressed Fas. Interleukin-1 beta (IL- 1 beta), abundantly produced in HT glands, induced Fas expression in n ormal thyrocytes, and cross-linking of Fas resulted in massive thyrocy te apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-s ensitive targets. Exposure to IL-1 beta induced thyrocyte apoptosis, w hich was prevented by antibodies that block Fas, suggesting that IL-1 beta-induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contr ibute to clinical hypothyroidism.