Inhibitory oligodeoxynucleotides - therapeutic promise for systemic autoimmune diseases?
Recent studies have shed new light on a possible link between the innate activation of plasmocytoid dendritic cells and marginal zone B cells and the pathogenesis of systemic lupus erythematosus. Animal studies have identified that this response requires the Toll-like receptor 9 (TLR9). Engagement of the TLR9 by various ligands, including non-canonical CpG-motifs, can cause or aggravate pathogenic autoantibody production and cytokine secretion in lupus. Attempts to neutralize this activity either by blocking the acidification of the endosomal compartment with chloroquine and related compounds, or by preventing the interaction between the CpG-DNA sequences and TLR9 using inhibitory oligonucleotides could be a promising therapeutic option for lupus.
Lenert
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Division of Rheumatology, Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA. petar-lenert@uiowa.edu
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D018899:CpG Islands / Q000276:immunology; D004247:DNA / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy; D009841:Oligonucleotides / Q000276:immunology* / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000276:immunology; D051217:Toll-Like Receptor 9
D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA