2007年7月
Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance
BLOOD
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- 巻
- 110
- 号
- 1
- 開始ページ
- 242
- 終了ページ
- 250
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1182/blood-2006-11-059980
- 出版者・発行元
- AMER SOC HEMATOLOGY
Although receptor activator of nuclear factor (NF)-kappa B 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-kappa B 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.
- リンク情報
- ID情報
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- DOI : 10.1182/blood-2006-11-059980
- ISSN : 0006-4971
- PubMed ID : 17371940
- Web of Science ID : WOS:000247611000037