title: The expression and function of the neonatal Fc receptor in thyrocytes of Hashimoto's thyroiditis.
abstract: OBJECTIVE
  Thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies (TgAb and TPOAb), which are primarily of the immunoglobulin G (IgG) class, can mediate antibody-dependent cell-mediated cytotoxicity in vitro. However, it is unclear whether any thyrocyte molecules can facilitate the transport and elimination of TgAb and TPOAb. The IgG transport receptor neonatal Fc receptor (FcRn) is a candidate mediator of these processes. In this study, we aimed to evaluate FcRn expression and function in normal and Hashimoto's thyroiditis (HT) thyrocytes.
  
  
  METHODS
  FcRn expression in primary thyrocyte cultures (four normal and four HT groups) was examined by polymerase chain reaction (PCR) and Western blotting. Localization of FcRn was demonstrated by immunoelectron microscopy. A double immunofluorescence staining method was adopted to detect FcRn and internalized human TgAb IgG. Stimulation experiments were performed to assess the regulation of FcRn expression by T helper cell 1 (Th1) (IFN-γ and TNF-α) and Th2 cytokines (IL-10 and IL-4).
  
  
  RESULTS
  FcRn expression was lower in HT thyrocytes than in normal thyrocytes. FcRn was located in the cytoplasm, membranes, mitochondria and transport vesicles of thyrocytes. Both human IgG and TgAb IgG were internalized by thyrocytes in a pH-dependent manner and co-localized with FcRn in thyrocytes. FcRn expression was downregulated by Th1 and Th2 cytokines in both normal and HT thyrocytes in a dose-dependent manner.
  
  
  CONCLUSIONS
  Our results suggest that FcRn may be associated with the transport and metabolism of IgG in thyrocytes and that transport is independent of IgG type. FcRn may be involved in HT pathogenesis.
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Chenxu
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Civil Aviation General Hospital, No. 1 Gao Jing Jia Street, Chao Yang District, Beijing 100123, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China. Electronic address: emilyzy14@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Guizhi
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Guo
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006111:Graves Disease / Q000276:immunology / Q000378:metabolism*; D050031:Hashimoto Disease / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007453:Iodide Peroxidase / Q000276:immunology; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D013954:Thyroglobulin / Q000276:immunology; D000072637:Thyroid Epithelial Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D013954:Thyroglobulin; D007453:Iodide Peroxidase; C100688:Fc receptor, neonatal
keywords: Hashimoto's thyroiditis; IgG; Neonatal Fc receptor; TgAb; Th1/Th2 cytokines