DECTIN-2 regulates macrophage M1 polarization via the SYK/ROS/JNK axis to influence the progress of apical periodontitis.

DECTIN-2 belongs to the C-type lectin receptor (CLR) family and is mainly detected on macrophages, dendritic cells, and additional immune cell populations, where it modulates immune and inflammatory functions. However, its role in macrophage polarization and apical periodontitis remains to be elucidated. Given the critical role of macrophage polarization in inflammation, our study aimed to investigate the function and underlying mechanisms of DECTIN-2 in macrophage polarization and apical periodontitis. This study revealed enhanced M1 polarization of macrophages in human apical periodontitis lesions, accompanied by significantly upregulated DECTIN-2 expression through single-cell sequencing analysis. In vitro experiments demonstrated that Dectin-2 knockdown inhibited macrophage polarization toward the M1 phenotype, whereas Dectin-2 overexpression promoted this process. Furthermore, in a Dectin-2 knockout mouse model of apical periodontitis, M1 macrophage polarization was significantly suppressed with reduced inflammation in the periapical region and markedly attenuated bone destruction. Mechanistically, transcriptomic sequencing analysis combined with functional validation demonstrated that DECTIN-2 activates the SYK kinase to promote reactive oxygen species (ROS) production by upregulating NOX2 expression, thereby activating the JNK signaling pathway and ultimately driving M1 polarization of macrophages. In summary, this study reveals that DECTIN-2 regulates M1 polarization of macrophages through the SYK/ROS/JNK signaling axis, thereby influencing the progression of apical periodontitis. These findings provide new mechanistic understanding and identify potential therapeutic avenues for apical periodontitis.