Bloch Y, et al., 48(1):45-58.e6, Immunity, 2018
Interleukin-23 (IL-23) is a pro-inflammatory human cytokine, which is closely associated with many autoimmune and inflammatory diseases. Reported herein is the crystal structure of human IL-23 in complex with its cognate receptor, IL-23R. Furthermore, a mechanism has been proposed to explain how IL-23 gets activated by IL-23R to mediate a tripartite complex with interleukin-12 receptor subunit β1 (IL-12Rβ1). Bio-Layer Interferometry (BLI) was used to assess the binding affinity of IL-23, and its mutant variants to murine IL-23R (mIL-23R). A Pall ForteBio Octet RED96 instrument equipped with Anti-Human IgG Fc (AHQ) Biosensor probes were used to perform all BLI assays. AHQ sensor tips were immobilized with mIL-23R Fc and dipped in 3-fold dilution series of various cytokines for an association step, followed by a dissociation step in assay buffer. Biosensors were regenerated after each cycle by using glycine (pH 1.75). BLI data obtained were fitted to a 1:1 binding model. The kinetic rate constants (ka and kd) and the equilibrium dissociation constants (KD values) were determined for all binding interactions. Collectively, the structural and mechanistic findings of this investigation may provide additional therapeutic avenues to address the broad spectrum of diseases linked to IL-23.