Toll-like receptors: potential targets for lupus treatment

Acta Pharmacol Sin. 2015 Dec;36(12):1395-407. doi: 10.1038/aps.2015.91. Epub 2015 Nov 23.

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the loss of tolerance to self-nuclear antigens. Accumulating evidence shows that Toll-like receptors (TLRs), previously proven to be critical for host defense, are implicated in the pathogenesis of autoimmune diseases by recognition of self-molecules. Genome-wide association studies, experimental mouse models and clinical sample studies have provided evidence for the involvement of TLRs, including TLR2/4, TLR5, TLR3 and TLR7/8/9, in SLE pathogenesis. A number of downstream proteins in the TLR signaling cascade (such as MyD88, IRAKs and IFN-α) are identified as potential therapeutic targets for SLE treatment. Numerous antagonists targeting TLR signaling, including oligonucleotides, small molecular inhibitors and antibodies, are currently under preclinical studies or clinical trials for SLE treatment. Moreover, the emerging new manipulation of TLR signaling by microRNA (miRNA) regulation shows promise for the future treatment of SLE.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies / therapeutic use
  • Drug Discovery / methods*
  • Humans
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • MicroRNAs / therapeutic use
  • Molecular Targeted Therapy / methods*
  • Oligonucleotides / therapeutic use
  • Signal Transduction / drug effects
  • Small Molecule Libraries / therapeutic use
  • Toll-Like Receptors / antagonists & inhibitors
  • Toll-Like Receptors / immunology*

Substances

  • Antibodies
  • MicroRNAs
  • Oligonucleotides
  • Small Molecule Libraries
  • Toll-Like Receptors