Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis

作者：Jinmei Zhang, Qiong Ding, Angela X. Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T. Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu L. Lei, Shaoping Zhang · 发表于：Life Sciences · 年份：2025 · DOI：10.1016/j.lfs.2025.123559 · 被引用次数：6 · 研究领域：Oral microbiology and periodontitis research、Immune Response and Inflammation、Inflammasome and immune disorders

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in an exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid lineage-specific IFN-I response was essential in safeguarding against periodontal inflammation by suppressing the IL-17-producing γδ T cells in gingiva. IFN-I signaling also directly repressed osteoclastogenesis in monocytes, which are precursor cells for osteoclasts. Therefore, our findings demonstrate that an integral myeloid-specific IFN-I pathway protects against bone loss by keeping the IL-17-neutrophil axis in check and directly inhibiting osteoclast formation in periodontitis.