Potential Involvement of Fas and Its Ligand in the Pathogenesis of Hashimoto's Thyroiditis

Abstract

The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1beta (IL-1beta), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contribute to clinical hypothyroidism.

Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto's thyroiditis

“…Intriguing experimental evidences from two independent groups suggested that apoptosis may be responsible for the thyroid cells destruction observed in HT (Giordano et al, 1997;Hammond et al, 1997;Stassi and De Maria, 2002). The proposed mechanism involves Fas, a member of the tumour necrosis factor receptor family.…”

TNF-α and IFN-γ Regulate Expression and Function of the Fas System in the Seminiferous Epithelium

“…Previously, we have demonstrated that inflammatory mediators enhance adhesion between Sertoli cells and lymphocytes by up-regulation of adhesion molecules specific for lymphocytes (4); this increased binding may favor Fas-mediated apoptosis of Sertoli cells, and a localized loss of Sertoli cells may cause a leakage of the blood-tubular barrier, hence leading to autoimmune orchitis. Previous reports have demonstrated the crucial regulatory role of the Fas system in the induction of autoimmune diseases such as Hashimoto's thyroiditis (44), rheumatic disease (45), and multiple sclerosis (46). In Hashimoto's thyroiditis, the IL-1␤-mediated induction of Fas on thyrocytes results in the immune response by lymphocytes and tissue homeostasis destruction by the thyrocytes themselves, which constitutively express FasL.…”

Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia

“…4 Binding of FasL to Fas or cross-linking of Fas with agonistic antibodies induces apoptosis in Fas-bearing cells. 12,26,27 On the other hand, TNF-␣ induces apoptosis and activates transcription factor NF-B. 12,27 Furthermore, TGF-␤ induced apoptosis in a myeloid leukemic cell line.…”