Fig. 3

NLRP3 inflammasome activation and somatic mosaicism. PAMPs, pathogen-associated molecular pattern molecules; DAMPs, damage-associated molecular patterns; TLR, toll-like receptor; TNFR, tumor necrosis factor receptor. A A simplified schema of the NLRP3 inflammasome activation is illustrated based on a previous study [35]. After NLRP3 inflammasome is activated, activated caspase 1 converts pro IL-1β to mature IL-1β and induces pore formation leading to pyroptosis via activation of gasdermin D. Activated IL-1β and other cytoplasmic materials are released through the pore, thus generated. B Comparison of germline mutation and somatic mosaicism. While heterozygous NLRP3 mutation in a zygotic cell is transmitted to all the somata, somatic mosaicism takes place by post-zygotic mutation in NLRP3 in CAPS and thus a small fraction of the somata carry the pathogenic NLRP3 variant. Cells with pathogenic NLRP3 variant are reported to spontaneously activate the inflammasome [36]