The signaling networks of the herpesvirus entry mediator (TNFRSF14) in immune regulation.
The tumor necrosis factor (TNF) receptor superfamily member herpesvirus entry mediator (HVEM) (TNFRSF14) regulates T-cell immune responses by activating both inflammatory and inhibitory signaling pathways. HVEM acts as both a receptor for the canonical TNF-related ligands, LIGHT [lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed on T lymphocytes] and lymphotoxin-α, and as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules. The ability of HVEM to interact with multiple ligands in distinct configurations creates a functionally diverse set of intrinsic and bidirectional signaling pathways that control both inflammatory and inhibitory responses. The HVEM system is integrated into the larger LTβR and TNFR network through extensive shared ligand and receptor usage. Experimental mouse models and human diseases indicate that dysregulation of HVEM network may contribute to autoimmune pathogenesis, making it an attractive target for drug intervention.
Laboratory of Molecular Immunology, Center for Infectious and Inflammatory Diseases, Sanford|Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Marcos W
MW
Steinberg
Timothy C
TC
Cheung
Carl F
CF
Ware
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000276:immunology; D020239:Receptor Cross-Talk / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1