Modulation of toll-like receptor function has therapeutic potential in autoimmune disease

Felix I L Clanchy, Sandra M Sacre
Expert Opinion on Biological Therapy 2010, 10 (12): 1703-16

IMPORTANCE OF THE FIELD: The role of toll-like receptors (TLRs) in the immune response to exogenous pathogens is well characterized. These receptors have been suggested to be involved in the initiation and/or perpetuation of many inflammatory autoimmune diseases and have become attractive candidates for the modulation of inflammation.

AREAS COVERED IN THIS REVIEW: This review discusses the evidence to support a potential role for TLRs in inflammatory diseases, focusing on rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. The approaches to targeting TLR activation are outlined.

WHAT THE READER WILL GAIN: An appreciation for the role of TLRs in inflammatory diseases and in particular the contribution of specific TLRs in rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. This review focuses on recent developments in targeting TLR activity from ligand binding through to the resultant signaling.

TAKE HOME MESSAGE: As initiators of immune responses, TLRs have previously been targeted to increase the immune response with some success. However, targeting TLRs to attenuate immune responses for the treatment of chronic inflammatory diseases will require further evidence of the mechanisms of TLR involvement in the pathophysiology and a better understanding of the potential effects of modulating TLR physiology over a sustained period.

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