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Role of toll-like receptors in systemic sclerosis

Published online by Cambridge University Press:  28 August 2013

Marzena Ciechomska ,
Rachel Cant ,
James Finnigan ,
Jacob M. van Laar  and
Steven O'Reilly
Marzena Ciechomska
Affiliation:
Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Rachel Cant
Affiliation:
Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
James Finnigan
Affiliation:
Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Jacob M. van Laar
Affiliation:
Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Steven O'Reilly*
Affiliation:
Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
*
*Corresponding author: Steven O'Reilly, Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. E-mail: steven.o'[email protected]
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Abstract

Accumulative evidence demonstrates the crucial role of evolutionary conserved Toll-like receptors (TLRs) in identifying microbial or viral compounds. TLRs are also able to recognise endogenous molecules which are released upon cell damage or stress and have been shown to play a key role in numerous autoimmune diseases including systemic sclerosis (SSc). A classic feature of SSc, is vascular injury manifested as Raynaud's phenomenon and ischaemia of the skin, resulting in the release of endogenous TLR ligands during inflammation and local tissue damage. These locally released TLR ligands bind TLRs possibly complexed to autoantibodies, and initiate intracellular signalling pathways and may be one of the mechanisms that initiate and drive autoimmunity and subsequent fibrosis. Activation of the immune system results in interferon (IFN) sensitive gene transcription. There is also an IFN gene signature in SSc peripheral blood. TLRs may represent the link between immune activation, common in SSc, and tissue fibrosis. Therefore, a better understanding of the mechanisms of TLR-mediated pathogenesis and therapies targeting individual TLRs, may provide a more specific approach of treating multi-systemic autoimmune diseases. This review aims to integrate the current knowledge of TLR function in the autoimmune disorders with particular emphasis on SSc. We suggest the TLR system as a new therapeutic target.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 15 , 2013 , e9
Copyright
Copyright © Cambridge University Press 2013 

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