‘Toll’ Gates for Future Immunotherapy

Author(s): Ken J. Ishii, Satoshi Uematsu, Shizuo Akira

Journal Name: Current Pharmaceutical Design

Volume 12 , Issue 32 , 2006

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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.

Keywords: Interleukin-1 receptor-associated kinase, Oligodeoxyribonucleic acids, TNF receptor-associated factor 6, immunological disorders, TLR antagonists

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Article Details

Year: 2006
Page: [4135 - 4142]
Pages: 8
DOI: 10.2174/138161206778743484
Price: $65

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