Regulating the mucosal immune system: the contrasting roles of LIGHT, HVEM, and their various partners

LIGHT and herpes virus entry mediator (HVEM) comprise a ligand–receptor pair in the tumor necrosis factor superfamily. These molecules play an important role in regulating immunity, particularly in the intestinal mucosa. LIGHT also binds the lymphotoxin β receptor, and HVEM can act as a ligand for immunoglobulin family molecules, including B- and T-lymphocyte attenuator, which suppresses immune responses. Complexity in this pivotal system arises from several factors, including the non-monogamous pairing of ligands and receptors, and reverse signaling or the ability of some ligands to serve as receptors. As a result, recognition events in this fascinating network of interacting molecules can have pro- or anti-inflammatory consequences. Despite complexity, experiments we and others are carrying out are establishing rules for understanding when and in what cell types these molecules contribute to intestinal inflammation.