Presentation: Immunoregulatory Role of RANKL-stimulated Dendritic Cells on Autoimmune Arthritis in MRL/lpr Mice (2007)

146 Immunoregulatory Role of RANKL-stimulated Dendritic Cells on Autoimmune Arthritis in MRL/lpr Mice

PURPOSE: Recent studies have established that receptor activator of NF-kB (RANK) /RANKL signaling plays a key role for maintenance of dendritic cells (DCs) in the periphery. However, the association of the RANKL signaling for DCs with autoimmunity has been obscure. In this study, we investigated the immunoregulatory role of DCs through RANKL signaling on autoimmune arthritis using MRL/lpr mice. METHODS: The phenotypes and functions were analyzed using DCs of spleen and lymph nodes, or bone marrow-derived DCs (BMDCs) from MRL/lpr and MRL+/+ mice. The surface markers on the peripheral DCs and RANKL-stimulated BMDCs were analyzed by flow cytometer. Apoptosis- and cell cycle-related molecules of the DCs were detected by Western blot analysis. In addition, the adaptive transfer of RANKL-stimulated BMDCs was performed into MRL/lpr mice as recipients to modulate the arthritis lesions. RESULTS: We found that the number of CD11c+CD11b+CD8a+myeloid DCs in the periphery from MRL/lpr mice was significantly increased comparing with that from control mice, and that the MRL/lpr DCs could survive much longer than control DCs. In addition, the expressions of Bcl-x and Bcl-2 and the nuclear transport of NF-kB of RANKL-stimulated BMDCs from MRL/lpr mice were considerably upregulated compared with those from control mice. On the other hands, Fas expression of normal BMDCs was significantly increased by RANKL stimulation. Moreover, the adoptive transfer of RANKL-stimulated BMDCs resulted in accelerated and severe autoimmune arthritis of MRL/lpr recipients. CONCLUSIONS: These findings suggest that the crosstalk between RANKL and Fas signaling in DCs might influence the maintenance of DCs in the periphery and the development of autoimmunity.

 T. Izawa, None; N. Ishimaru, None; K. Moriyama, None; Y. Hayashi, None.