Journal of Clinical and Cellular Immunology
Open Access

Abstract

Role of Fas and RANKL Signaling in Peripheral Immune Tolerance

Takashi Izawa, Rieko Arakaki and Naozumi Ishimaru

The death receptor, Fas, has been well-characterized and is a critical factor in apoptosis in immune cells. Fas also has an important role in maintaining immune tolerance as demonstrated in the autoimmune-prone MRL/lpr mouse strain which carries a defect in Fas-mediated apoptosis of T cells. However, the role of Fas-independent apoptosis remains to be characterized in autoimmune diseases. In dendritic cells (DCs), binding of receptor activator of nuclear factor-κB ligand (RANKL) to RANK perpetuates the survival of mature DCs. However, cross-talk between the RANK/RANKL pathway and Fas-mediated signaling during the function or activation of DCs has not been well-studied. This short communication review describes a mechanism involving interactions between activated DCs and T cells in the autoimmune response of MRL/lpr mice and a novel Fas-independent apoptosis pathway in T cells that maintains peripheral tolerance, and controls autoimmunity in MRL/lpr mice.