KAT6A Promotes Macrophage Inflammation and Periodontitis

Both epigenetic modification and immunoregulation play important roles in periodontitis (PD). However, the function of macrophage lysine acetyltransferase 6A (KAT6A) in PD remains unknown. In this study, we first analysed single-cell RNA sequencing data and demonstrated up-regulated KAT6A expression in periodontal tissue macrophages of PD patients. Subsequently, macrophage KAT6A knockout (MK6AKO) mice were generated and subjected to PD induction by a combination of molar ligation and application of Porphyromonas gingivalis (Pg). Morphological analyses showed significantly decreased alveolar bone resorption in MK6AKO mice, and qRT-PCR analysis showed markedly attenuated expression of inflammatory genes in the gingiva of MK6AKO mice compared to littermate mice after PD induction. RNA-seq of peritoneal macrophages stimulated with Pg lipopolysaccharides (Pg-LPS) unveiled down-regulation of inflammatory pathways, particularly the interleukin 17 pathway in MK6AKO macrophages. Flow cytometry analysis detected a notable reduction of neutrophils in the gingiva of MK6AKO mice after PD induction. Furthermore, using the Cut&tag technique, we identified reduced histone H3K27 acetylation levels at nuclear factor kappa-B binding sites on promoters of interleukin 1β and tumour necrosis factor in MK6AKO macrophages treated with Pg-LPS. In summary, our study highlights the significant role of KAT6A in modulating macrophage phenotypes and the progression of PD, suggesting the therapeutic potential of targeting KAT6A.