Spatiotemporal regulation of acute wound healing by the NLRP3 inflammasome: dual roles in macrophage-fibroblast chemotaxis and phenotype during wound repair

NLRP3 exerts dual-phase regulatory roles in wound healing: (i) during inflammation, it drives chemokine-mediated macrophage/fibroblast recruitment and M1 polarization while suppressing fibroblast-mediated repair via IL-1β signaling; (ii) later, NLRP3 deficiency enhances Wnt/Notch signaling, promoting structural restoration despite transiently delayed healing. Moreover, fibroblasts with high NLRP3 expression engage an inflammasome-independent NLRP3/ROS axis that augments activation of TGF-β/Smad signaling. These findings position NLRP3 as a potential therapeutic target for modulating phase-specific inflammatory and regenerative responses.