Interleukin-18 receptor alpha (IL-18Rα)

Interleukin-18 receptor alpha is a cytokine receptor that constitutes the ligand-binding component of the heterodimeric IL-18 receptor (alongside IL-18 receptor beta co-receptor). It belongs to the interleukin-1 receptor family and is expressed primarily on hematopoietic cells (such as NK cells, T cells, and some B cells) and at lower levels in some non-immune cells. Upon binding interleukin-18, IL-18Rα forms a low affinity complex which, with recruitment of IL-18Rβ, triggers high-affinity interaction and initiates downstream intracellular signaling involving MyD88, IRAK, TRAF6, and ultimately NF-κB activation. This process promotes expression of multiple inflammatory cytokines and mediators, playing a pivotal role in innate and adaptive immune responses and linking to several inflammatory and immune-related diseases. Targeting the IL-18–IL-18Rα pathway is under investigation for the treatment of autoimmune diseases, chronic inflammatory conditions, and some forms of cancer, with most interventions focusing on cytokine blockade rather than inhibition of the receptor itself.

Other names

IL-18RαIL18R1 (gene name)Interleukin-1 receptor-related protein (IL-1Rrp)CD218a (in some immunological nomenclatures)

Blockade of IL-18 signaling by neutralizing IL-18 (e.g., monoclonal antibodies or recombinant IL-18BP); Inhibition of receptor-ligand interaction (prevents IL-18/IL-18Rα complex formation); Downregulation of downstream NF-κB and pro-inflammatory signaling