Spatiotemporal analysis of periodontitis—the unique role of the IL-33/ST2 axis

Periodontitis, which is induced by repeated bacterial invasion and the ensuing immune reactions that follow, is the leading cause of tooth loss. However, studies on immune responses are usually based on gingival tissue, although periodontal tissue is actually comprised of four different components. Here, we have developed a novel model to analyze the pathogenesis of periodontitis with different periodontal tissue components. We have found that the inflammatory response in the peri-root tissues and the expression of interleukin (IL)-6 and nuclear factor κ-Β ligand (RANKL) by Thy-1.2 – fibroblasts/stromal cells were prominent during the course of bone destruction. Furthermore, a comprehensive analysis of the initiation phase confirmed these findings while revealing a high level of expression of ST2 (also known as IL33R and encoded by Il1rl1 ) in the peri-root tissue. Il1rl1 and Il33 deficient mice exhibited exacerbated bone loss in the acute phase of periodontitis, demonstrating the protective role of the IL-33/ST2 axis in acute inflammation. Thus, the findings obtained with this novel model show the crucial role of the peri-root tissue and advance our understanding of the etiology of periodontitis.