Analysis of Apoptosis in Relation to Tissue Destruction Associated With Hashimoto's Autoimmune Thyroiditis

Hammond, L. J.; Lowdell, Mark W.; Cerrano, Paolo G.; Goode, A W; Bottazzo, G. F.; Mirakian, Rita

doi:10.1002/(sici)1096-9896(199706)182:2<138::aid-path810>3.0.co;2-f

Cited by 80 publications

(58 citation statements)

References 31 publications

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“…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.…”

Section: Discussionmentioning

confidence: 97%

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

Gasbarri

Sciacchitano²,

Marasco

et al. 2004

Br J Cancer

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Hashimoto's thyroiditis (HT) represents the most common cause of hypothyroidism and nonendemic goiter, but its clinical and pathological heterogeneity opens the question if this disease should be more properly considered as a spectrum of different thyroid conditions rather than as a single nosological entity. In this study, we analysed 133 cases of HT for the expression of galectin-3, a lectin molecule involved in malignant transformation, apoptosis and cell cycle control. An unexpected expression of galectin-3 was demonstrated in a subset of HT together with the presence of HBME-1, c-met and cyclin-D1 that are also involved in malignant transformation and deregulated cell growth. Furthermore, a loss of allelic heterozygosity in a specific cancer-related chromosomal region was demonstrated in some HT harbouring galectin-3-positive follicular cells, by using laser capture microdissection. On the basis of the morphological and molecular findings we identified four subsets of HT: (a) HT with classic features of chronic autoimmune thyroiditis; (b) HT associated to hyperplastic/adenomatous lesions; (c) HT harbouring thyroid cancer precursors; (d) HT associated to unequivocal thyroid microcarcinomas. Our findings provide a well-substantiated morphological and molecular demonstration that HT may include a spectrum of different thyroid conditions ranging from chronic autoimmune thyroiditis to thyroiditis triggered by specific immune-response to cancer-related antigens.

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Section: Discussionmentioning

confidence: 97%

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

Gasbarri

Sciacchitano²,

Marasco

et al. 2004

Br J Cancer

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“…Thyrocytes function as stimulatory APCs to T cells in vitro (Eguchi, et al, 1995;Eguchi et al, 1988;Matsuoka et al, 1996;Nagataki and Eguchi, 1992), and Fas ϩ Ag-presenting B cells are killed by Ag-specific CD4 ϩ FasL ϩ T cell clone (Ozdemirli et al, 1996). Although Fas is expressed in situ on thyrocytes in patients with Graves' disease, apoptosis of these cells is reported to be suppressed, as determined by in situ end-labeling of fragmented DNA (Hammond et al, 1997;Tanimoto et al, 1995), indicating that humoral factors such as TSAb inhibit Fas/FasL interactions between thyrocytes and activated CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

“…The percentage of apoptotic thyrocytes in situ is increased in Hashimoto's thyroiditis, but decreased in Graves' disease (Giordano et al, 1997;Hammond et al, 1997;Tanimoto et al, 1995), suggesting the importance of apoptotic cell death of thyrocytes in the regulation of functions and numbers of these cells in autoimmune thyroid diseases.…”

mentioning

confidence: 99%

“…Immunohistological studies have revealed Fas expression on thyrocytes in patients with Graves' disease and Hashimoto's thyroiditis (Giordano et al, 1997;Hammond et al, 1997;Tanimoto et al, 1995). We recently reported that Fas is functionally expressed on human thyrocytes in vitro, and Fas-mediated apoptosis of these cells by anti-Fas IgM is significantly suppressed by the addition of TSH or TSAb containing IgG (Kawakami et al, 1997b).…”

mentioning

confidence: 99%

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CD4+ T Cell-Mediated Cytotoxicity Toward Thyrocytes: The Importance of Fas/Fas Ligand Interaction Inducing Apoptosis of Thyrocytes and the Inhibitory Effect of Thyroid-Stimulating Hormone

Kawakami

Matsuoka

Tsuboi

et al. 2000

Laboratory Investigation

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SUMMARY:The accumulation of activated CD4 ϩ T cells and antigen (Ag)-dependent cellular interactions between thyrocytes and CD4 ϩ T cells have been determined in thyroid gland from patients with Graves' disease. The Fas/Fas ligand (FasL) interaction between antigen-presenting cells and T cells regulates the apoptosis of the former cells triggered by the latter cells. The inhibition of Fas-mediated apoptosis in thyrocytes could be a underlying mechanism of hyperplasia of thyrocytes in patients with Graves' disease. We investigated the potential role of Fas/FasL interaction between thyrocytes and CD4 ϩ T cells in the induction of Fas-mediated apoptosis of the former cells induced by the latter cells. The presence of only a few specific T cells responsive to a putative autoantigen has hampered the investigation of specific T cell activation toward antigen-presenting cells (APCs). Therefore, we used a superantigen, staphylococcal enterotoxin B (SEB), to examine specific T cell activation toward thyrocytes in vitro since it stimulates a large proportion of T cells with particular V␤ elements. Spontaneous apoptosis of thyrocytes in culture was not found even in the presence of various kinds of cytokines. In contrast, a clear induction of Fas-mediated apoptosis by anti-Fas IgM was determined in interferon-␥ (IFN-␥)-stimulated thyrocytes. In addition, a significant cytotoxicity of purified CD4 ϩ T cells toward IFN-␥-stimulated thyrocytes in the presence of SEB was induced, and the addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or blockade of the Fas/FasL interaction reduced this cytotoxicity. FasL expression of CD4 ϩ T cells cocultured with IFN-␥-stimulated thyrocytes in the presence of SEB was clearly induced. Furthermore, the addition of mAbs against CD54 and CD58 inhibited both cytotoxicity and FasL expression of CD4 ϩ T cells. The cytotoxicity of CD4 ϩ T cells toward IFN-␥-stimulated, SEB-pulsed thyrocytes was markedly inhibited when we used thyrocytes cultured with IFN-␥ in the presence of thyroid-stimulating hormone (TSH) as target cells. Our results suggest that 1) CD4 ϩ T cells were activated by thyrocytes expressing MHC class II molecules in an SEB-dependent manner and then expressed FasL. 2) These activated FasL ϩ CD4 ϩ T cells killed thyrocytes by interacting with Fas on thyrocytes and FasL on activated CD4 ϩ T cells. The presence of costimulating molecules such as CD54 and CD58 on thyrocytes was also necessary to generate activated FasL ϩ CD4 ϩ T cells. 3) Since the actions of thyroid stimulating antibody (TSAb) toward thyrocytes are similar to those of TSH, one goitrogenic activity of TSAb may, in part, be due to the inhibitory effect on Fas-mediated apoptosis of thyrocytes triggered by activated CD4 ϩ T cells. (Lab Invest 2000, 80:471-484).

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“…In thyrocyte cultures, Fas protein was detected either by antibodies against Fas antigen (24,41,42), or by Western blots in cell lysates (41). However, it was recently reported that Fas expression is induced on thyrocytes only under the influence of inflammatory cytokines, such as interferon-g (IFN-g) or IL-1b (29).…”

Section: Regulation Of the Fas Pathway In The Thyroid Glandmentioning

confidence: 99%

The role of Fas-mediated apoptosis in thyroid disease

Andrikoula

Tsatsoulis

2001

European Journal of Endocrinology

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Recent evidence has emphasized the importance of apoptosis in the maintenance of tissue homeostasis and the pathogenesis of malignant and immune diseases. Autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease, as well as other autoimmune endocrine diseases, have been associated with dysregulation of apoptotic signaling pathways. In particular, dysfunction of the Fas apoptotic pathway or production of soluble factors including soluble Fas and soluble Fas ligand may be involved in the pathogenesis of these disorders. On the other hand, malignant thyroid cells may avoid Fas-mediated suicide possibly by expression of inhibitors of apoptosis and evade the immune system by inducing apoptosis on infiltrating lymphocytes. The delicate balance between cell proliferation and cell death through the Fas pathway may also play an important role in the control of thyroid cell mass and goitrogenesis. This review analyzes the current evidence on the role of Fasmediated apoptosis in the pathogenesis of thyroid diseases including Hashimoto's thyroiditis, Graves' disease, thyroid cancer and goiter. However, the exact mechanisms involved in the regulation of apoptosis in thyroid disease remain unclear. Further investigation is needed.

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Analysis of Apoptosis in Relation to Tissue Destruction Associated With Hashimoto's Autoimmune Thyroiditis

Cited by 80 publications

References 31 publications

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

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

CD4+ T Cell-Mediated Cytotoxicity Toward Thyrocytes: The Importance of Fas/Fas Ligand Interaction Inducing Apoptosis of Thyrocytes and the Inhibitory Effect of Thyroid-Stimulating Hormone

The role of Fas-mediated apoptosis in thyroid disease

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