Periodontitis is a global disease burden, underpinned by chronic inflammation, driven by microbial dysbiosis and an exaggerated host immune response, leading to irreversible destruction of the supporting structures of the teeth. Emerging evidence have revealed that features consistent with trained immunity are present in periodontitis, including hyper-responsive circulating monocytes and altered neutrophil behaviour. In particular, monocyte-derived macrophages display a heightened inflammatory state, contributing to excessive cytokine release, oxidative damage, and osteoclast-mediated bone loss, yet the mechanisms sustaining this hyper-inflammatory phenotype remain poorly defined.
Vitamin D deficiency is associated with increased severity of periodontal disease and increased tooth loss. Vitamin D is a potent immunomodulator that regulates epigenetic and metabolic pathways central to trained immunity; however, its impact on macrophage-trained immunity and its ability to reverse maladaptive immune memory remain unclear. This PhD project will test the central hypothesis that vitamin D modulates trained immunity in macrophages by reshaping their epigenetic and metabolic programming, thereby restoring a balanced inflammatory and antibacterial phenotype and enabling the therapeutic reversal of established trained immunity and periodontitis-induced alveolar bone loss.
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