Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus

Arthritis Res Ther. 2006;8(1):203. doi: 10.1186/ar1888. Epub 2006 Jan 10.


This review focuses on the role of Toll-like receptors (TLRs) in lupus and on possibilities to treat lupus using TLR modulating inhibitory oligodeoxynucleotides (INH-ODNs). TLRs bridge innate and adaptive immune responses and may play an important role in the pathogenesis of systemic lupus erythematosus. Of particular interest are TLR3, -7, -8, and -9, which are localized intracellularly. These TLRs recognize single-stranded or double-stranded RNA or hypomethylated CpG-DNA. Exposure to higher order CpG-DNA ligands or to immune complexed self-RNA triggers activation of autoreactive B cells and plasmacytoid dendritic cells. INH-ODNs were recently developed that block all downstream signaling events in TLR9-responsive cells. Some of these INH-ODNs can also target TLR7 signaling pathways. Based on their preferential cell reactivity, we classify INH-ODNs into class B and class R. Class B ('broadly reactive') INH-ODNs target a broad range of TLR-expressing cells. Class R ('restricted') INH-ODNs easily form DNA duplexes or higher order structures, and are preferentially recognized by autoreactive B cells and plasmacytoid dendritic cells, rather than by non-DNA specific follicular B cells. Both classes of INH-ODNs can block animal lupus. Hence, therapeutic application of these novel INH-ODNs in human lupus, particularly class R INH-ODNs, may result in more selective and disease-specific immunosuppression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autoimmunity
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Dendritic Cells / metabolism*
  • Humans
  • Lupus Vulgaris / drug therapy*
  • Oligonucleotides, Antisense / therapeutic use*
  • Plasma Cells / metabolism*
  • Signal Transduction*
  • Toll-Like Receptors / genetics*
  • Toll-Like Receptors / metabolism


  • Oligonucleotides, Antisense
  • Toll-Like Receptors