Crosstalk between RANKLand Fas signaling in dendritic cells controls immune tolerance

Takashi Izawa, Naozumi Ishimaru, Keiji Moriyama, Masayuki Kohashi, Rieko Arakaki, Yoshio Hayashi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Although receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling has been shown to prolong the survival of mature dendritic cells (DCs), the association of RANKL pathway with Fas-mediated apoptosis is obscure. Here, we found that bone marrow-derived DCs (BMDCs) from the Fas-deficient strain MRL/lpr mice, could survive much longer than normal DCs. The expressions of Bcl-x and Bcl-2 and the nuclear transport of NF-κB of RANKL-stimulated BMDCs from MRL/lpr mice were significantly upregulated. By contrast, Fas expression of BMDCs from normal C57BL/6 and MRL+/+ mice was increased by RANKL stimulation, and an enhanced DC apoptosis was found when stimulated with both RANKL and anti-Fas mAb, which was associated with activation of caspase-3 and caspase-9. Furthermore, the expression of FLIPL, an inhibitory molecule against Fas-mediated apoptosis, in normal DCs was significantly decreased by RANKL and anti-Fas mAb. Indeed, the adoptive transfer of RANKL-stimulated DCs resulted in rapid acceleration of autoimmunity in MRL/lpr recipients. These findings indicate that the crosstalk between RANKL and Fas signaling in DCs might control immune tolerance.

Original languageEnglish
Pages (from-to)242-250
Number of pages9
Issue number1
Publication statusPublished - Jul 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Crosstalk between RANKLand Fas signaling in dendritic cells controls immune tolerance'. Together they form a unique fingerprint.

Cite this