title: Demonstration of innate immune responses in the thyroid gland: potential to sense danger and a possible trigger for autoimmune reactions.
abstract: BACKGROUND
  Autoimmune thyroid disease is an archetypal organ-specific autoimmune disorder that is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid. However, the underlying mechanisms by which specific thyroid antibodies are produced are largely unknown. Recent studies have shown that innate immune responses affect both the phenotype and the severity of autoimmune reactions. Moreover, it appears that even non-immune cells, including thyroid cells, have an ability to launch such responses. The aim of this study was to conduct a more detailed analysis of innate immune responses of the thyroid upon stimulation with various "non-self" and "self" factors that might contribute to the initiation of autoimmune reactions.
  
  
  METHODS
  We used rat thyroid FRTL-5 cells, human thyroid cells, and mice to investigate the effects of various pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and iodide on gene expression and function that were related to innate immune responses.
  
  
  RESULTS
  RT-PCR analysis showed that both rat and human thyroid cells expressed mRNAs for Toll-like receptors (TLRs) that sensed PAMPs. Stimulation of thyrocytes with TLR ligands resulted in activation of the interferon-beta (IFN-β) promoter and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-dependent promoter. As a result, pro-inflammatory cytokines, chemokines, and type I interferons were produced. Similar activation was observed when thyroid cells were stimulated with double-stranded DNA, one of the typical DAMPs. In addition to these PAMPs and DAMPs, treatment of thyroid cells with high concentrations of iodide increased mRNA expression of various cytokines.
  
  
  CONCLUSIONS
  We show that thyroid cells express functional sensors for exogenous and endogenous dangers, and that they are capable of launching innate immune responses without the assistance of immune cells. Such responses may relate to the development of thyroiditis, which in turn may trigger autoimmune reactions.
authors.affiliation: Laboratory of Molecular Diagnostics, Department of Mycobacteriology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akama
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshihara
authors.forename: Mariko
authors.initials: M
authors.lastname: Sue
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanigawa
authors.forename: Huhehasi
authors.initials: H
authors.lastname: Wu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishido
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeshita
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishii
authors.forename: Kanji
authors.initials: K
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016899:Interferon-beta / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013959:Thyroid Diseases / Q000276:immunology* / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051193:Toll-Like Receptors; D016899:Interferon-beta