title: ER stress impairs MHC Class I surface expression and increases susceptibility of thyroid cells to NK-mediated cytotoxicity.
abstract: We recently reported that, in thyroid cells, ER stress triggered by thapsigargin or tunicamycin, two well known ER stressing agents, induced dedifferentiation and loss of the epithelial phenotype in rat thyroid cells. In this study, we sought to evaluate if, in thyroid cells, ER stress could affect MHC class I expression and the possible implications of this effect in the alteration of function of natural killer cells, suggesting a role in thyroid pathology. In both, a human line of fetal thyroid cells (TAD-2 cells) and primary cultures of human thyroid cells, thapsigargin and tunicamicin triggered ER stress evaluated by BiP mRNA levels and XBP-1 splicing. In both cell types, TAD-2 cell line and primary cultures, major histocompatibility complex class I (MHC-I) plasmamembrane expression was significantly reduced by ER stress. This effect was accompanied by signs of natural killer activation. Thus, natural killer cells dramatically increased IFN-γ production and markedly increased their cytotoxicity against thyroid cells. Together, these data indicate that ER stress induces a decrease of MHC class I surface expression in thyroid cells, resulting in reduced natural killer-cell self-tolerance.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ulianich
authors.forename: G
authors.initials: G
authors.lastname: Terrazzano
authors.forename: M
authors.initials: M
authors.lastname: Annunziatella
authors.forename: G
authors.initials: G
authors.lastname: Ruggiero
authors.forename: F
authors.initials: F
authors.lastname: Beguinot
authors.forename: B
authors.initials: B
authors.lastname: Di Jeso
mesh_terms: D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D058767:Protein Unfolding; D019284:Thapsigargin / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology*; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D015395:Histocompatibility Antigens Class I; D014415:Tunicamycin; D019284:Thapsigargin; D007371:Interferon-gamma