Taking Two TRAILS

The TNF-related apoptosis-inducing ligand (TRAIL) has well-described anti-inflammatory effects in models of autoimmune disease, including experimental autoimmune encephalomyelitis (EAE). In this issue of Neuron, Aktas, Smorodchenko, and colleagues present evidence that TRAIL exerts anti-inflammatory effects, but also induces neuronal apoptosis, in EAE. This report poses the therapeutic challenge of facilitating TRAIL expression in the periphery while inhibiting TRAIL in the CNS.