Spatiotemporal Regulation of Acute Wound Healing by the NLRP3 Inflammasome: Dual Roles in Macrophage-Fibroblast Chemotaxis and Phenotype During Wound Repair

January 2026 in “ Burns & Trauma ”

Dongzhen Zhu, JianJun Li, Bingyang Yu, Nanbo Liu, Xu Guo, Yanlin Su, Yuzhen Wang, Yun Huang, Liting Liang, Linhao Hou, Chao Zhang, Qinghua Liu, Mengde Zhang, Wei Song, Yi Kong, Jinpeng Du, Zhao Li, Yue Kong, Feng Tian, Xiangye Yin, Ping Zhu, Xiaobing Fu, Sha Huang

NLRP3 inflammasome macrophage fibroblast chemotaxis M1 polarization chemokine-mediated pathways IL-1β signaling Wnt/Notch signaling TGF-β/Smad signaling ROS axis

TLDR NLRP3 helps control inflammation and repair in wound healing, making it a potential target for treatment.

The study explores the dual roles of the NLRP3 inflammasome in wound healing, focusing on macrophage-fibroblast chemotaxis and phenotype modulation. NLRP3 is crucial for timely wound closure by regulating inflammation and cell recruitment, primarily through IL-1β signaling. However, its absence in knockout mice leads to improved tissue repair quality, including enhanced hair follicle formation and reduced fibrosis. The research highlights NLRP3's role in macrophage phenotype switching and fibroblast function, suggesting it as a potential therapeutic target for modulating inflammation and promoting tissue regeneration. Despite its benefits in acute repair, prolonged NLRP3 activity can impair healing in chronic wounds, indicating the need for phase-specific therapeutic strategies. The study involved both human and mouse models, analyzing 58,814 cells from human wounds and using CRISPR-Cas9-generated knockout mice.