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 .
Subcellular locations: Cytoplasm, 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 .