title: 'Toll' gates for future immunotherapy.
abstract: Toll-like receptors (TLRs) are evolutionary conserved transmembrane proteins that recognize a unique pattern of molecules derived from pathogens or damaged cells, triggering robust but defined innate immune responses. TLR-mediated innate and/or adaptive immune responses play an important role in a variety of diseases including infectious diseases, sepsis, autoimmune diseases, allergy, and atherosclerosis. Each TLR displays a differential expression pattern, intracellular localization and signaling pathway, resulting in distinct immune responses. A variety of new TLR ligands including agonists (e.g. urinary Tamm-Horsfall glycoprotein as a TLR4 ligand, siRNA as TLR3 or 7 ligand, Plasmodium falciparum Hemozoin as a TLR9 ligand, Profilin-like protein in Toxoplasma gondii as a TLR11 ligand) and antagonists (G-rich oligodeoxynucleotides as antagonist for TLR9) have been identified, and some of other TLR ligands are already under clinical trials. The manipulation or intervention of TLR-mediated immune responses is a possible multiple 'Toll' gate for future developments of immunotherapies.
authors.affiliation: Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency (JST), Suita, Osaka 565-0871, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D007167:Immunotherapy / Q000639:trends*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D051193:Toll-Like Receptors