Interleukin-18 receptor (IL-18R) (IL-18R)

The Interleukin-18 receptor (IL-18R) is a heteromeric cytokine receptor belonging to the Interleukin-1 receptor superfamily, primarily expressed on T cells, natural killer (NK) cells, and dendritic cells (UniProt Consortium, 2023). It consists of two subunits: the IL-18R alpha chain (IL-18Rα), which serves as the ligand-binding component, and the IL-18R beta chain (IL-18Rβ), which is essential for signal transduction (NCBI Gene, 2024). Upon binding its ligand, Interleukin-18 (IL-18), the receptor recruits the adapter protein MyD88, initiating a signaling cascade that activates NF-κB and mitogen-activated protein kinases (MAPK). This process significantly enhances the production of interferon-gamma (IFN-γ) and promotes the polarization of Th1 immune responses (PubMed: 30449319). In modern oncology, IL-18R is a critical focal point for next-generation CAR-T cell therapies; by engineering CAR-T cells to secrete IL-18, researchers aim to activate the IL-18R on both the CAR-T cells themselves and on endogenous bystander immune cells within the tumor microenvironment (Hu et al., 2017). This dual activation helps to remodel the immunosuppressive tumor milieu, increasing the persistence and anti-tumor efficacy of the treatment, though systemic activation must be carefully managed to avoid severe inflammatory toxicities (StatPearls, 2023).

Other names

IL18RCD218Interleukin-1 receptor-related proteinIL-1RrpCD218a/b

Agonism of the IL-18 receptor complex triggers the MyD88-dependent signaling pathway, activating NF-κB and MAPK cascades to induce interferon-gamma production and enhance T-cell and NK-cell effector functions (Avanzi et al., 2018).