Cutting edge: Fas ligand (CD178) cytoplasmic tail is a positive regulator of Fas ligand-mediated

The cytotoxic function of CD178 (Tas ligand (FasL)) is critical to the maintenance of peripheral tolerance and immune-mediated tissue pathology. The active site of FasL resides at the FasL extracellular region (FasL(Ext)) and it functions through binding/cross-linking Fas receptor on target cells. In this study, we report that FasL(Ext)-mediated cytotoxicity is regulated by the FasL cytoplasmic tail (Fas(LCyt)). Deleting the N-terminal 2-70 aa (Delta 70) or N-terminal 2-33 aa (Delta 33) reduced the cytotoxic strength as much as 30- to 100-fold. By contrast, change in the cytotoxic strength was not observed with FasL deleted of the proline-rich domains (45-74 aa, Delta PRD) in the FasL(Cyt) Our study identifies a no velfunction of FasL(Cyt) and demonstrates that FasL(Cyt), a sequence unique to FasL, is critically required for the optimal expression of FasL(Ext)-mediated cytotoxicity.