Fas receptor (FAS) (FAS)

The Fas receptor, also known as CD95 or Tumor necrosis factor receptor superfamily member 6, is a critical cell surface death receptor that regulates immune system homeostasis by inducing apoptosis (UniProt, 2024). Upon binding to its ligand, FasL (CD178), the receptor oligomerizes and recruits the Fas-associated death domain (FADD) protein, which in turn activates the caspase cascade, specifically caspase-8 and caspase-3, leading to programmed cell death (Peter & Krammer, 2003). This mechanism is vital for the deletion of activated T-lymphocytes after an immune response has been mounted, thereby preventing chronic inflammation and autoimmunity (Akiyama et al., 2012). In therapeutic applications, umbilical cord-derived mesenchymal stem cells (UC-MSCs) utilize surface-expressed FasL to engage the Fas receptor on overactive T-cells, effectively inducing their apoptosis and promoting immune tolerance in conditions like graft-versus-host disease (Gao et al., 2014). While the Fas pathway is a potent target for immunomodulation, its clinical utility has been historically hampered by the risk of severe hepatotoxicity, as hepatocytes are highly sensitive to Fas-mediated death signals (Waring & Mullbacher, 1999). Modern approaches, including cell-based therapies and localized agonists, aim to harness this pathway while minimizing systemic side effects.

Other names

CD95Tumor necrosis factor receptor superfamily member 6APO-1APT1FAS1TNFRSF6

Agonism of the Fas receptor on activated T-lymphocytes triggers the extrinsic apoptotic pathway via FADD recruitment and caspase-8 activation, leading to the depletion of effector T-cells and subsequent immunosuppression (Akiyama et al., 2012; Peter & Krammer, 2003).