PlumX Metrics
Embed PlumX Metrics

IL-18 receptors, their role in ligand binding and function: Anti-IL-1RAcPL antibody, a potent antagonist of IL-18

Journal of Immunology, ISSN: 0022-1767, Vol: 165, Issue: 9, Page: 4950-4956
2000
  • 72
    Citations
  • 0
    Usage
  • 47
    Captures
  • 2
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

IL-18 is critical in eliciting IFN-γ production from Th1 cells both in vitro and in vivo. Th1 cells have been implicated in the pathogenesis of autoimmune disorders, making antagonists of IL-18 promising therapeutics, However, specificity and binding characteristics of IL-18R components have only been superficially explored. In this study, we show that IL-1R related protein 1 (IL-1Rrp1) and IL-1R accessory protein-like (IL-1RAcPL) confer responsiveness to IL-18 in a highly specific (no response to other IL-1 ligands) and unique manner (no functional pairing with other IL-1Rs and IL-1R-like molecules). Cotransfection with both receptor components resulted in expression of both low and high affinity binding sites for IL-18 (K(d) of 11 and 0.4 nM, respectively). We prepared anti-IL-1RAcPL mAb TC30-28E3, which, in contrast to soluble R proteins, effectively inhibited the IL-18-induced activation of NF-κB. Quantitative PCR showed that Th1 but not Th2 cells are unique in that they coexpress IL-1Rrp1 and IL-1RAcPL. mAb TC30-28E3 inhibited IL-18-induced production of IFN-γ by Th1 cells, being at least 10-fold more potent than anti-IL-18 ligand mAb. This study shows that IL-1RAcPL is highly specific to IL-18, is required for high affinity binding of IL-18, and that the anti-IL-1RAcPL mAb TC30-28E3 potently antagonizes IL-18 responses in vitro, providing a rationale for the use of anti-IL-1RAcPL Abs to inhibit Th1-mediated inflammatory pathologies.

Bibliographic Details

Reno Debets; Jackie C. Timans; Tatyana Churakowa; Sandra Zurawski; Rene de Waal Malefyt; Kevin W. Moore; John S. Abrams; Anne O’Garra; J. Fernando Bazan; Robert A. Kastelein

Oxford University Press (OUP)

Medicine; Immunology and Microbiology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know