Periodontitis as an “osteoimmune” disease

Abstract: Periodontitis, one of the most common infectious diseases in humans, is a unique “osteoimmune” disease in which antibacterial immune response causes alveolar bone destruction. In 1972, Horton et al. reported that immune cells stimulated by the dental plaque derived from periodontitis patients produce osteoclast-activating factors, providing the first evidence for the osteoimmune dialogue (Horton et al., Science 1972). However, although the pioneering work in the field of osteoimmunology was conducted in the context of periodontitis, the mechanisms and the role of osteoimmune interaction in periodontitis have been largely unclear until fairly recently. Using a newly established murine periodontitis model, we showed that the crosstalk between immune and bone cells at the oral barrier plays a critical role in the pathogenesis of periodontitis. Bacterial invasion leads to the generation of specialized immune cells that protect against bacteria by evoking mucosal immune responses as well as inducing bone damage, the latter of which may also contribute to the host defense by removing the infected-tooth. These findings suggest that inflammatory bone destruction, which has been regarded merely as an adverse secondary effect of inflammation, may have evolved as a part of host defense machinery against oral microbiota (Tsukasaki et al., Nature Commun 2018, Nature Rev Immunol 2019). To understand the pathogenesis of and develop future therapeutic strategies for periodontal bone loss, it is vitally important to clarify precise molecular mechanisms underlying osteoclastic bone erosion. Recently, we unveiled the importance of the tight regulation of RANKL activity by the local OPG production in bone and immune systems by generating OPG-floxed mice (Tsukasaki et al., Cell Rep in press), and deciphered the stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution (Tsukasaki et al., Nature Metabolism in revision). In this talk, I will summarize the recent progress of the osteoimmunology field and provide a new perspective on the periodontology from the osteoimmunological standpoint.