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

Giorgio Stassi, Diana Di Liberto, Matilde Todaro, Ann Zeuner, Lucia Ricci-Vitiani, Antonella Stoppacciaro, Luigi Ruco, Felicia Farina, Giovanni Zummo, Ruggero De Maria

Research output: Contribution to journalArticle

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 andTH2 cytokines controls thyrocyte survival in thyroid autoimmunity.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalNature Immunology
Volume1
Issue number6
Publication statusPublished - Dec 2000

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins'. Together they form a unique fingerprint.

  • Cite this

    Stassi, G., Di Liberto, D., Todaro, M., Zeuner, A., Ricci-Vitiani, L., Stoppacciaro, A., Ruco, L., Farina, F., Zummo, G., & De Maria, R. (2000). Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins. Nature Immunology, 1(6), 483-488.