Major histocompatibility class II HLA-DRα gene expression in thyrocytes: Counter regulation by the class II transactivator and the thyroid y box protein

Valeria Montani, Shinichi Taniguchi, Minho Shong, Koichi Suzuki, Masayuki Ohmori, Cesidio Giuliani, Giorgio Napolitano, Bruno Fiorentino, Andreas M. Reimold, Jenny P Y Ting, Leonard D. Kohn, Dinah S. Singer

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27 Scopus citations

Abstract

Aberrant expression of major histocompatibility complex (MHC) class II proteins on thyrocytes, which is associated with autoimmune thyroid disease, is mimicked by γ-interferon (γ-IFN). To define elements and factors that regulate class II gene expression in thyrocytes and that might be involved in aberrant expression, we have studied γ-IFN-induced HLA-DRα gene expression in rat FRTL-5 thyroid cells. The present report shows that class II expression in FRTL-5 thyrocytes is positively regulated by the class II transactivator (CIITA), and that CIITA mimics the action of γ-IFN. Thus, as is the case for γ-IFN, several distinct and highly conserved elements on the 5'-flanking region of the HLA-DRα gene, the S, X1, X2, and Y boxes between -137 to -65 bp, are required for class II gene expression induced by pCIITA transfection in FRTL-5 thyroid cells. CIITA and γ-IFN do not cause additive increases in HLA-DRα gene expression in FRTL-5 cells, consistent with the possibility that CIITA is an intermediate factor in the γ-IFN pathway to increased class II gene expression. Additionally, γ-IFN treatment of FRTL-5 cells induces an endogenous CIITA transcript; pCIITA transfection mimics the ability of γ-IFN treatment of FRTL-5 thyroid cells to increase the formation of a specific and novel protein/DNA complex containing CBP, a coactivator of CRE binding proteins important for cAMP-induced gene expression; and the action of both γ-IFN and CIITA to increase class II gene expression and increase complex formation is reduced by cotransfection of a thyroid Y box protein, which suppresses MHC class I gene expression in FRTL-5 thyroid cells and is a homolog of human YB-1, which suppresses MHC class II expression in human glioma cells. We conclude that CIITA and TSH receptor suppressor element binding protein-1 are components of the γ-IFN-regulated transduction system which, respectively, increase or decrease class II gene expression in thyrocytes and may, therefore, be involved in aberrant class II expression associated with autoimmune thyroid disease.

Original languageEnglish (US)
Pages (from-to)280-289
Number of pages10
JournalEndocrinology
Volume139
Issue number1
DOIs
StatePublished - 1998

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Montani, V., Taniguchi, S., Shong, M., Suzuki, K., Ohmori, M., Giuliani, C., Napolitano, G., Fiorentino, B., Reimold, A. M., Ting, J. P. Y., Kohn, L. D., & Singer, D. S. (1998). Major histocompatibility class II HLA-DRα gene expression in thyrocytes: Counter regulation by the class II transactivator and the thyroid y box protein. Endocrinology, 139(1), 280-289. https://doi.org/10.1210/endo.139.1.5673