Il18

Function

Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses. Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells. 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.

Post-translational modifications

The pro-IL-18 precursor is processed by CASP1 to yield its mature, active form. The pro-IL-18 precursor is however not processed by Casp4/Casp11 in rodents (By similarity). The pro-IL-18 precursor features autoinhibitory interactions between the propeptide and the post-cleavage-site region, preventing recognition by the IL18R1 receptor. Processing by CASP1 induces conformational changes to generate critical receptor-binding sites. The mature form is then secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore. In contrast, cleavage by CASP3 inactivates IL18 (By similarity).

Sequence Similarities

Belongs to the IL-1 family.

Cellular localization

• Cytoplasm
• Cytosol
• Secreted
• The precursor is cytosolic. In response to inflammasome-activating signals, cleaved and secreted. Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore. In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation. The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10.

Alternative names

Igif, Il18, Interleukin-18, IL-18, Interferon gamma-inducing factor, Interleukin-1 gamma, IFN-gamma-inducing factor, IL-1 gamma

Database links

swissprot:P97636 entrezGene:29197

Other research areas

• Immuno-oncology