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Toll-like receptors and chronic inflammation in rheumatic diseases: new developments

Leo A B Joosten1,2, Shahla Abdollahi-Roodsaz3,4, Charles A Dinarello1,5

  • 1Department of Internal Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, Netherlands.

Nature Reviews. Rheumatology
|May 13, 2016
PubMed

Insights

New research highlights Toll-like receptors (TLRs) in rheumatic diseases. Understanding TLR signalling, ligands, and inhibitors offers new therapeutic strategies for inflammatory joint conditions like rheumatoid arthritis and lupus.

Area of Science:

  • Immunology
  • Rheumatology
  • Molecular Biology

Background:

  • Toll-like receptors (TLRs) play a crucial role in chronic inflammation observed in various rheumatic diseases.
  • Recent advancements have elucidated the inhibitory function of TLR10 and identified novel TLR-enhancing receptors and inhibitors.
  • Emerging evidence links the microbiome and TLRs to the pathogenesis of rheumatic diseases.

Purpose of the Study:

  • To review recent findings on the involvement of Toll-like receptors (TLRs) in inflammatory joint diseases.
  • To focus on the signalling mechanisms, particularly the Toll-IL-1 receptor (TIR) domain, and the ligands that activate TLRs.
  • To discuss current and potential future therapeutic strategies targeting TLR signalling in rheumatic diseases.

Main Methods:

  • Literature review of recent developments in TLR research related to rheumatic diseases.
  • Analysis of studies focusing on TLR signalling pathways, including the TIR domain.
  • Examination of research on exogenous and endogenous ligands for TLRs.
  • Review of therapeutic strategies targeting TLRs in conditions such as rheumatoid arthritis, systemic lupus erythematosus, gout, and Lyme arthritis.

Main Results:

  • Novel insights into the function of TLR10 as an inhibitor have been reported.
  • Identification of receptors that enhance TLR function and specific TLR inhibitors.
  • The significant role of the microbiome in the context of TLRs and rheumatic disease onset is increasingly recognized.
  • Detailed understanding of TLR signalling mechanisms, including TIR domain interactions and ligand binding.

Conclusions:

  • Toll-like receptors (TLRs) are central players in the pathogenesis of inflammatory rheumatic diseases.
  • Targeting TLR signalling pathways, including their ligands and inhibitors, presents promising therapeutic avenues.
  • Further research into TLRs, the microbiome, and their interplay is crucial for developing effective treatments for conditions like rheumatoid arthritis, lupus, gout, and Lyme arthritis.

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