Type I Interferon Protects Against Bone Loss in Periodontitis by Mitigating an Interleukin (Il)-17-Neutrophil Axis

Authors

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 Leo Lei
Shaoping Zhang

Language

English

Publication Date

6-15-2025

Journal

Life Science

DOI

10.1016/j.lfs.2025.123559

PMID

40086745

PMCID

PMC12094266

PubMedCentral® Posted Date

6-15-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Interleukin-17, Periodontitis, Animals, Humans, Mice, Neutrophils, Alveolar Bone Loss, Male, Interferon Type I, Mice, Inbred C57BL, Female, Gingival Crevicular Fluid, Signal Transduction, Osteoclasts, Interferon-beta, Type-I interferon (IFN-I), Periodontitis, Neutrophil, Interleukin-17 (IL-17), Osteoclastogenesis, Monocytes, Single-cell analysis

Published Open-Access

yes

Recommended Citation

Zhang, Jinmei; Ding, Qiong; Wang, Angela X; et al., "Type I Interferon Protects Against Bone Loss in Periodontitis by Mitigating an Interleukin (Il)-17-Neutrophil Axis" (2025). Faculty, Staff and Student Publications. 6094.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6094