Therapeutic targeting of Toll-like receptors

Toll-like receptors (TLRs) play a crucial role in innate immune response in mammals. Individual TLRs recognize microbial components that are conserved among pathogens and activate their signaling pathways. Each TLR has its own cascade of signaling pathway for exhibiting its specific responses through selective utilization of TIR domain-containing adaptors. Increasing evidence for roles of TLRs in various diseases provides us new insights for a basis of new therapies. In this review, we discuss the possibilities of therapeutics targeting TLRs in various diseases and explain potential problems associated with such approaches. Martin Braddock – AstraZeneca R&D Charnwood, Loughborough, UK Ian Adcock – Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, UK Immune-modulation represents an exciting a potential very rich area for the development of pharmacological agents in a wide variety of immune-mediated diseases. The Toll receptor family recognise specific ligands which may function as agonists or antagonists and which serve to modulate receptor signalling via a complex intra-cellular pathway. This pathway involves many mediators, some of which are targets for drug therapy such as members of the MAP kinase family. A detailed understanding of the role of these receptors and their ligands in the innate and acquired immune response will demonstrate their true value as promising drug targets for future therapies.