NLRC4: detecting bacterial invasion machinery
Function
NAIP proteins recognize bacterial flagellin or type-III secretion-system components and recruit NLRC4 to assemble an inflammasome. Caspase-1 activation then promotes IL-1-family cytokine maturation and pyroptotic defense.
NAIP–NLRC4 intact
Invasive bacterial structures can trigger rapid epithelial/innate defense.
→
NLRC4 lost
Defense against relevant pathogens may weaken; excessive inflammatory injury may also fall.
NLRC4 and NLRP3 are not redundant synonyms: their upstream triggers differ. Hypomethylation in severe UC may mark immune-cell abundance or regulatory change, but it does not demonstrate inflammasome activity.
What is distinctive about NLRC4
NAIPs provide ligand recognition and nucleate NLRC4 oligomerization; bacterial flagellin and type-III-secretion-system proteins are canonical triggers. Reactome curates this neighborhood as the IPAF inflammasome (Milacic, Beavers, Conley, and others, 2024). The response can rapidly activate caspase-1 and expel or kill infected cells. Human and mouse NAIP repertoires differ, so ligand specificity cannot always be transferred directly between species.
Relevance and evidence gap in UC
NLRC4 is biologically plausible where barrier breach increases bacterial access, but a severe-UC DMR does not identify ligand, assembled complex, or cellular source. Demonstrating the pathway requires sensor-specific stimulation or complex capture alongside cleaved caspase-1, gasdermin D, IL-18/IL-1β, and epithelial versus myeloid localization. Without those measurements, the locus is an inflammatory-context marker.