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[Apoptosis and the thyroid: the Fas pathway].

V Vlaeminck-Guillem1, M d'Herbomez-Boidein, M Decoulx

  • 1Clinique Endocrinologique Marc Linquette, USNA, CHRU de Lille.

Presse Medicale (Paris, France : 1983)
|March 14, 2001
PubMed
Summary

The Fas/Fas-L pathway regulates thyroid cell death. Dysregulation contributes to thyroid diseases like Hashimoto

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Area of Science:

  • Immunology
  • Cell Biology
  • Endocrinology

Background:

  • The Fas/Fas-L pathway is a key mediator of apoptosis, involving Fas receptor on target cells and Fas ligand on cytotoxic cells.
  • Thyroid gland volume is regulated by thyroid-stimulating hormone (TSH) and thyrocyte apoptosis, with normal thyrocytes expressing Fas but not Fas-L.
  • Thyrocytes possess resistance mechanisms to Fas-mediated apoptosis, involving inhibitors of apoptotic signal transduction.

Purpose of the Study:

  • To investigate the role of the Fas/Fas-L apoptotic pathway in normal thyroid physiology and various thyroid pathologies.
  • To elucidate the mechanisms of thyrocyte apoptosis regulation in Hashimoto's thyroiditis, Graves' disease, and thyroid cancer.

Main Methods:

  • Analysis of Fas and Fas-L expression and function in thyroid cells and infiltrating lymphocytes in different thyroid conditions.
  • Assessment of apoptotic pathways and signaling in normal thyrocytes, and in thyrocytes from patients with thyroiditis and cancer.
  • Correlation of soluble Fas levels with the clinical course of Graves' disease.

Main Results:

  • In Hashimoto's thyroiditis, thyrocytes aberrantly express Fas-L, leading to fratricide apoptosis, while infiltrating lymphocytes are apoptosis-resistant (Bcl2 overexpression).
  • In Graves' disease, reduced thyrocyte apoptosis and goiter formation are linked to repressed Fas expression and increased soluble Fas, correlating with disease activity.
  • Thyroid cancer cells exhibit resistance to apoptosis and induce apoptosis in antitumoral lymphocytes via Fas counter-attack.

Conclusions:

  • The Fas/Fas-L pathway plays a critical, albeit complex, role in thyroid homeostasis and pathogenesis.
  • Aberrant Fas/Fas-L signaling contributes to thyrocyte loss in Hashimoto's thyroiditis and influences disease progression in Graves' disease.
  • Fas-mediated apoptosis evasion is a hallmark of thyroid cancer, enabling tumor growth and immune evasion.

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