Title: ‘Toll’ Gates for Future Immunotherapy
VOLUME: 12 ISSUE: 32
Author(s):Ken J. Ishii, Satoshi Uematsu and Shizuo Akira
Affiliation:Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka,Suita, Osaka 565-0871, Japan.
Keywords:Interleukin-1 receptor-associated kinase, Oligodeoxyribonucleic acids, TNF receptor-associated factor 6, immunological disorders, TLR antagonists
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. TLRmediated 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.
