Network communications: lymphotoxins, LIGHT, and TNF.
Lymphotoxins (LT) provide essential communication links between lymphocytes and the surrounding stromal and parenchymal cells and together with the two related cytokines, tumor necrosis factor (TNF) and LIGHT (LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), form an integrated signaling network necessary for efficient innate and adaptive immune responses. Recent studies have identified signaling pathways that regulate several genes, including chemokines and interferons, which participate in the development and function of microenvironments in lymphoid tissue and host defense. Disruption of the LT/TNF/LIGHT network alleviates inflammation in certain autoimmune disease models, but decreases resistance to selected pathogens. Pharmacological disruption of this network in human autoimmune diseases such as rheumatoid arthritis alleviates inflammation in a significant number of patients, but not in other diseases, a finding that challenges our molecular paradigms of autoimmunity and perhaps will reveal novel roles for this network in pathogenesis.
Ware
Carl F
CF
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA. cware@liai.org
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D015398:Signal Transduction; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; C505914:TNFSF14 protein, human; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha