Category: immune_innate
Multi-protein cytoplasmic complex activated by danger signals (urate crystals, cholesterol crystals, ATP, β-amyloid, viral RNA). Two-signal model: Signal 1 (priming) — TLR/NF-κB upregulates NLRP3 + pro-IL-1β + pro-IL-18 transcripts. Signal 2 (activation) — NLRP3 oligomerizes + recruits ASC + procaspase-1 → autoactivation → CASPASE-1. Outputs: (1) cleaves pro-IL-1β + pro-IL-18 to mature cytokines → secretion. (2) Cleaves gasdermin D (GSDMD) → N-terminus oligomerizes in plasma membrane → pyroptotic pore + cytokine release + cell death. Disease: gout (urate crystals), atherosclerosis (cholesterol crystals; CANTOS canakinumab trial showed CV event reduction); CAPS (CIAS1/NLRP3 GOF mutations; treated with anakinra IL-1RA, rilonacept IL-1 trap, or canakinumab anti-IL-1β mAb).