IL-18

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).

The pro-IL-18 precursor is processed by CASP1 to yield its mature, active form (PubMed:37993712, PubMed:37993714). The pro-IL-18 precursor is however not processed by Casp4/Casp11 in rodents (PubMed:37993712, PubMed:37993714). The pro-IL-18 precursor features autoinhibitory interactions between the propeptide and the post-cleavage-site region, preventing recognition by the IL18R1 receptor (By similarity). Processing by CASP1 induces conformational changes to generate critical receptor-binding sites (By similarity). The mature form is then secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (By similarity). In contrast, cleavage by CASP3 inactivates IL18 (By similarity).

Belongs to the IL-1 family.

• Cytoplasm
• Secreted
• The precursor is cytosolic (By similarity). In response to inflammasome-activating signals, cleaved and secreted (By similarity). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:30392956). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (By similarity). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (By similarity).

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

• entrezGene:16173
• swissprot:P70380

Proteins

Immunology & Infectious Disease

• Immuno-oncology

22135Da