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Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins

Nature Immunology volume 1, pages 483–488 (2000)Cite this article

Abstract

After autoimmune inflammation, interactions between CD95 and its ligand (CD95L) mediate thyrocyte destruction in Hashimoto's thyroiditis (HT). Conversely, thyroid autoimmune processes that lead to Graves' disease (GD) result in autoantibody-mediated thyrotropin receptor stimulation without thyrocyte depletion. We found that GD thyrocytes expressed CD95 and CD95L in a similar manner to HT thyrocytes, but did not undergo CD95-induced apoptosis either in vivo or in vitro. This pattern was due to the differential production of TH1 and TH2 cytokines. Interferon γ promoted caspase up-regulation and CD95-induced apoptosis in HT thyrocytes, whereas interleukin 4 and interleukin 10 protected GD thyrocytes by potent up-regulation of cFLIP and Bcl-xL, which prevented CD95-induced apoptosis in sensitized thyrocytes. Thus, modulation of apoptosis-related proteins by TH1 and TH2 cytokines controls thyrocyte survival in thyroid autoimmunity.

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Figure 1: Expression of CD95L and CD95 in autoimmune thyrocytes.
Figure 2: Resistance to apoptosis of GD thyrocytes.
Figure 3: Expression of pro-apoptotic and anti-apoptotic factors in autoimmune and nonautoimmune thyrocytes.
Figure 4: Pro-apoptotic and anti-apoptotic effect of TH1 and TH2 cytokines on thyrocytes.
Figure 5: Inhibition of CD95-induced apoptosis in thyrocytes by Bcl-xL and cFLIP.

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Acknowledgements

Supported by grants from AIRC (to R. D. M.) and Telethon-Italy, grant number E.735 (to G. S.). D. D. L. is a recipient of a Telethon fellowship. A. Z. is a recipient of a FIRC fellowship. We thank M. Catalano for excellent technical support.

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Authors and Affiliations

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

    Giorgio Stassi, Diana Di Liberto, Matilde Todaro, Felicia Farina & Giovanni Zummo

  2. Institute of General Pathology, University of Catania, Istituto Superiore di Sanità, Italy

    Ann Zeuner & Ruggero De Maria

  3. Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Italy

    Ann Zeuner, Lucia Ricci-Vitiani & Ruggero De Maria

  4. Department of Experimental Medicine and Pathology University of Rome “La Sapienza”, Italy

    Antonella Stoppacciaro & Luigi Ruco

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  1. Giorgio Stassi
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Correspondence to Ruggero De Maria.

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Stassi, G., Di Liberto, D., Todaro, M. et al. Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins. Nat Immunol 1, 483–488 (2000). https://doi.org/10.1038/82725

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