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Fas-FasL in Hashimoto's Thyroiditis

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Abstract

Hashimoto's thyroiditis is a common chronic autoimmune disease characterized by the loss of thyroid follicular cells (thyrocytes) that are gradually replaced by lymphocytic infiltration and diffuse fibrosis. These morphological findings suggested that autoreactive T-cell clones were responsible for thyrocyte destruction and hypothyroidism through effector–target cytotoxic recognition. Later, autonomous interaction between thyrocyte Fas and FasL has been proposed as a major mechanism of thyrocyte depletion in Hashimoto's thyroiditis. Here, we analyze the possible role of Fas and FasL in the pathogenesis of Hashimoto's thyroiditis. We suggest that the Fas–FasL system dictates the outcome of the autoimmune response by acting on both immune and target cells.

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REFERENCES

  1. Weetman AP, McGregor AM: Autoimmune thyroid disease: further developments in our understanding. Endocr Rev 15:788–830, 1994

    PubMed  Google Scholar 

  2. Dayan CM, Daniels GH: Chronic autoimmune thyroiditis. N Engl J Med 335:99–107, 1996

    PubMed  Google Scholar 

  3. Tanimoto C, Hirakawa S, Kawasaki H, Hayakawa N, Ota Z: Apoptosis in thyroid diseases: a histochemical study. Endocrinol J 42:193–201, 1995

    Google Scholar 

  4. Kotani T, Aratake Y, Hirai K, Fukazawa Y, Sato H, Ohtaki S: Apoptosis in thyroid tissue from patients with Hashimoto's thyroiditis. Autoimmunity 20:231–236, 1995

    PubMed  Google Scholar 

  5. Hammond LJ, Lowdell MW, Cerrano PG, Goode AW, Bottazzo GF, Mirakian R: Analysis of apoptosis in relation to tissue destruction associated with Hashimoto's autoimmune thyroiditis. J Pathol 182:138–144, 1997

    PubMed  Google Scholar 

  6. Bottazzo GF, Pujol-Borrell R, Hanafusa T, Feldmann M: Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2:1115–1119, 1983

    PubMed  Google Scholar 

  7. Weetman AP, McGregor AM: Autoimmune thyroid disease: Developments in our understanding. Endocrinol Rev 5:309–355, 1984

    Google Scholar 

  8. Tomer Y, Davies TF: Infection, thyroid disease, and autoimmunity. Endocrinol Rev 14:107–120, 1993

    Google Scholar 

  9. Del Prete GF, Vercelli D, Tiri A, Maggi E, Mariotti S, Pinchera A, Ricci M, Romagnani S: In vivo activated cytotoxic T cells in the thyroid infiltrate of patients with Hashimoto's thyroiditis. Clin Exp Immunol 65:140–147, 1986

    PubMed  Google Scholar 

  10. Londei M, Bottazzo GF, Feldmann M: Human T-cell clones from autoimmune thyroid glands: Specific recognition of autologous thyroid cells. Science 228:85–89, 1985

    PubMed  Google Scholar 

  11. Bottazzo GF, Drexhage HA, Khoury EL: Thyroid antibodies in thyroid diseases. Ciba Found Symp 90:153–177, 1982

    PubMed  Google Scholar 

  12. Czarnocka B, Ruf J, Ferrand M, Carayon P, Lissitzky S: Purification of the human thyroid peroxidase and its identification as the microsomal antigen involved in autoimmune thyroid diseases. FEBS Lett 190:147–152, 1985

    PubMed  Google Scholar 

  13. Weetman AP, Black CM, Cohen SB, Tomlinson R, Banga JP, Reimer CB: Affinity purification of IgG subclasses and the distribution of thyroid autoantibody reactivity in Hashimoto's thyroiditis. Scand J Immunol 30:73–82, 1989

    PubMed  Google Scholar 

  14. Chiovato L, Bassi P, Santini F, Mammoli C, Lapi P, Carayon P, Pinchera A: Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis. J Clin Endocrinol Metab 77:1700–1705, 1993

    PubMed  Google Scholar 

  15. Bogner U, Schleusener H, Wall JR: Antibody-dependent cellmediated cytotoxicity against human thyroid cells in Hashimoto's thyroiditis but not Graves' disease. J Clin Endocrinol Metab 59:734–738, 1984

    PubMed  Google Scholar 

  16. Leithauser F, Dhein J, Mechtersheimer G, Koretz K, Bruderlein S, Henne C, Schmidt A, Debatin KM, Krammer PH, Moller P: Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Invest 69:415–429, 1993

    PubMed  Google Scholar 

  17. Krammer PH: CD95(APO-1/Fas)-mediated apoptosis: Live and let die. Adv Immunol 71:163–210, 1999

    PubMed  Google Scholar 

  18. Nagata S: Fas ligand-induced apoptosis. Annu Rev Genet 33:29–55, 1999

    PubMed  Google Scholar 

  19. Pinkoski MJ, Green DR: Fas ligand, death gene. Cell Death Differ 6:1174–1181, 1999

    PubMed  Google Scholar 

  20. De Maria R, Testi R: Fas-FasL interactions: A common pathogenetic mechanism in organ-specific autoimmunity. Immunol Today 19:121–125, 1998

    PubMed  Google Scholar 

  21. Stassi G, De Maria R, Trucco G, Rudert W, Testi R, Galluzzo A, Giordano C, Trucco M: Nitric oxide primes pancreatic beta cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. J Exp Med 186:1193–1200, 1997

    PubMed  Google Scholar 

  22. Sabelko-Downes KA, Cross AH, Russell JH: Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis. J Exp Med 189:1195–1205, 1999

    PubMed  Google Scholar 

  23. Giordano C, Stassi G, De Maria R, Todaro M, Richiusa P, Papoff G, Ruberti G, Bagnasco M, Testi R, Galluzzo A: Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis. Science 275:960–963, 1997

    PubMed  Google Scholar 

  24. Borgerson KL, Bretz JD, Baker JR Jr: The role of Fas-mediated apoptosis in thyroid autoimmune disease. Autoimmunity 30:251–264, 1999

    PubMed  Google Scholar 

  25. Kawakami A, Eguchi K, Matsuoka N, Tsuboi M, Kawabe Y, Ishikawa N, Ito K, Nagataki S: Thyroid-stimulating hormone inhibits Fas antigen-mediated apoptosis of human thyrocytes in vitro. Endocrinology 137:3163–169, 1996

    PubMed  Google Scholar 

  26. Mitsiades N, Poulaki V, Kotoula V, Mastorakos G, Tseleni-Balafouta S, Koutras DA, Tsokos M: Fas/Fas ligand up-regulation and Bcl-2 down-regulation may be significant in the pathogenesis of Hashimoto's thyroiditis. J Clin Endocrinol Metab 83:2199–2203, 1998

    PubMed  Google Scholar 

  27. Stassi G, Todaro M, Bucchieri F, Stoppacciaro A, Farina F, Zummo G, Testi R, De Maria R: Fas/Fas ligand-driven T cell apoptosis as a consequence of ineffective thyroid immunoprivilege in Hashimoto's thyroiditis. J Immunol 162:263–267, 1999

    PubMed  Google Scholar 

  28. De Maria R, Lenti L, Malisan F, d'Agostino F, Tomassini B, Zeuner A, Rippo MR, Testi R: Requirement for GD3 ganglioside in CD95-and ceramide-induced apoptosis. Science 277:1652–1655, 1997

    Article  PubMed  Google Scholar 

  29. Roura-Mir C, Catalfamo M, Sospedra M, Alcalde L, Pujol-Borrell R, Jaraquemada D: Single-cell analysis of intrathyroidal lymphocytes shows differential cytokine expression in Hashimoto's and Graves' disease. Eur J Immunol 27:3290–3302, 1997

    PubMed  Google Scholar 

  30. Kawakami A, Eguchi K, Matsuoka N, Tsuboi M, Urayama S, Kawabe Y, Tahara K, Ishikawa N, Ito K, Nagataki S: Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema. Clin Exp Immunol 110:434–439, 1997

    PubMed  Google Scholar 

  31. Bretz JD, Rymaszewski M, Arscott PL, Myc A, Ain KB, Thompson NW, Baker JR Jr: TRAIL death pathway expression and induction in thyroid follicular cells. J Biol Chem 274:23627–23632, 1999

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical, Anatomical, and Oncological Sciences, Human Anatomy Section, University of Palermo, Palermo, 90127, Italy

    Giorgio Stassi, Diana Di Liberto & Matilde Todaro

  2. Laboratory of Hematology and Oncology, Istituto Superiore di Sanit`a, Rome, 00161, Italy

    Ann Zeuner, Lucia Ricci-Vitiani & Ruggero De Maria

Authors
  1. Giorgio Stassi
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  2. Ann Zeuner
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  3. Diana Di Liberto
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  4. Matilde Todaro
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  5. Lucia Ricci-Vitiani
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  6. Ruggero De Maria
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Stassi, G., Zeuner, A., Di Liberto, D. et al. Fas-FasL in Hashimoto's Thyroiditis. J Clin Immunol 21, 19–23 (2001). https://doi.org/10.1023/A:1006732713634

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  • DOI: https://doi.org/10.1023/A:1006732713634

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