RANK signaling induces interferon-stimulated genes in the fetal thymic stroma

Daisuke Ohshima, Junwen Qin, Hiroyasu Konno, Akihisa Hirosawa, Takuma Shiraishi, Hiromi Yanai, Yusuke Shimo, Miho Shinzawa, Nobuko Akiyama, Riu Yamashita, Kenta Nakai, Taishin Akiyama, Jun ichiro Inoue

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Medullary thymic epithelial cells (mTECs) are essential for thymic negative selection to prevent autoimmunity. Previous studies show that mTEC development is dependent on the signal transducers TRAF6 and NIK. However, the downstream target genes of signals controlled by these molecules remain unknown. We performed a microarray analysis on mRNAs down-regulated by deficiencies in TRAF6 or functional NIK in an in vitro organ culture of fetal thymic stromata (2DG-FTOC). An in silico analysis of transcription factor binding sites in plausible promoter regions of differentially expressed genes suggests that STAT1 is involved in TRAF6- and NIK-dependent gene expression. Indeed, the signal of RANK, a TNF receptor family member that activates TRAF6 and NIK, induces the activation of STAT1 in 2DG-FTOC. Moreover, RANK signaling induces the up-regulation of interferon (IFN)-stimulated gene (ISG) expression, suggesting that the RANKL-dependent activation of STAT1 up-regulates ISG expression. The RANKL-dependent expression levels of ISGs were reduced but not completely abolished in interferon α receptor 1-deficient (Ifnar1-/-) 2DG-FTOC. Our data suggest that RANK signaling induces ISG expression in both type I interferon-independent and interferon-dependent mechanisms.

Original languageEnglish
Pages (from-to)530-536
Number of pages7
JournalBiochemical and biophysical research communications
Volume408
Issue number4
DOIs
Publication statusPublished - 2011 May 20

Keywords

  • Autoimmune
  • Interferon
  • NF-kappaB
  • Signal
  • TNF receptor family
  • TRAF
  • Thymic epithelial cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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