| First Author | Izawa T | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 1 | Pages | 242-50 |
| PubMed ID | 17371940 | Mgi Jnum | J:145411 |
| Mgi Id | MGI:3834530 | Doi | 10.1182/blood-2006-11-059980 |
| Citation | Izawa T, et al. (2007) Crosstalk between RANKL and Fas signaling in dendritic cells controls immune tolerance. Blood 110(1):242-50 |
| abstractText | Although receptor activator of nuclear factor (NF)-kappaB 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-kappaB of RANKL-stimulated BMDCs from MRL/lpr mice were significantly up-regulated. 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 FLIP(L), 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. |
