Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis
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.
Authors
- Yu L. Lei (ORCID: https://orcid.org/0000-0002-9868-9824)
- Angela X. Wang
- Maoxuan Lin (ORCID: https://orcid.org/0000-0001-5191-1857)
- Kevin Moss (ORCID: https://orcid.org/0000-0003-2332-1774)
- Hongli Sun
- Julie T. Marchesan (ORCID: https://orcid.org/0000-0003-0610-3193)
- Erliang Zeng (ORCID: https://orcid.org/0000-0002-2891-6497)
- Jinmei Zhang
- Ning Yu (ORCID: https://orcid.org/0000-0002-3046-4338)
- Qiong Ding
- Shaoping Zhang (ORCID: https://orcid.org/0000-0003-3004-4023)
- Megumi A Williamson
- Di Miao
- Wei Shi (ORCID: https://orcid.org/0009-0003-0208-6012)
Institutions
- University of North Carolina at Chapel Hill (US)
- University of Iowa (US)
- Indiana University Health (US)
- Brigham and Women's Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- East Carolina University (US)
- Indiana University – Purdue University Indianapolis (US)
Publication Details
- Journal
- Life Sciences
- Published
- 2025-03-12
- DOI
- https://doi.org/10.1016/j.lfs.2025.123559
- Citations
- 5
- Primary Topic
- Oral microbiology and periodontitis research
- Type
- article
- Field-Weighted Citation Impact
- 7.33
Funders
- Colgate-Palmolive Company
- National Institutes of Health
- Holden Comprehensive Cancer Center, University of Iowa
- Roy J. and Lucille A. Carver College of Medicine, University of Iowa
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Environmental Health Sciences
- National Institute of Dental and Craniofacial Research