6kn9

Publication Abstract from PubMed

The interleukin-18 subfamily belongs to the interleukin-1 family and plays an important role in modulating innate and adaptive immune responses. Dysregulation of IL-18 has been implicated in or correlated with numerous diseases, including inflammatory diseases, autoimmune disorders, and cancer. Thus, blockade of IL-18 signaling may offer therapeutic benefits in many pathological settings. Here, we report the development of synthetic human antibodies that target human IL-18Rbeta and block IL-18-mediated IFN-gamma secretion by inhibiting NF-kappaB and MAPK dependent pathways. The crystal structure of a potent antagonist antibody in complex with IL-18Rbeta revealed inhibition through an unexpected allosteric mechanism. Our findings offer a novel means for therapeutic intervention in the IL-18 pathway and may provide a new strategy for targeting cytokine receptors.

A Synthetic Human Antibody Antagonizes IL-18Rbeta Signaling Through an Allosteric Mechanism.,Liu S, Miersch S, Li P, Bai B, Liu C, Qin W, Su J, Huang H, Pan J, Sidhu SS, Wu D J Mol Biol. 2020 Jan 15. pii: S0022-2836(20)30042-5. doi:, 10.1016/j.jmb.2020.01.012. PMID:31954129^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.