Recombinant Mouse Interleukin-18 (Il18)

Function

Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:26638072, PubMed:26638073). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (By similarity). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (By similarity). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:30392956)

Subcellular Location

Cytoplasm; Secreted

Subunit

Forms a ternary complex with ligand-binding receptor subunit IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane. Mature IL18 first binds to IL18R1 forming a low affinity binary complex, which then interacts with IL18RAP to form a high affinity ternary complex that signals inside the cell. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion

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• Nowarski R. et al. Epithelial IL-18 equilibrium controls barrier function in colitis. — Cell (2015)
• Hara H. et al. The NLRP6 inflammasome recognizes lipoteichoic acid and regulates Gram-positive pathogen infection. — Cell (2018)
• Devant P. et al. Structural insights into cytokine cleavage by inflammatory caspase-4. — Nature (2023)