Journal article
Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis
Life sciences (1973), Vol.371, 123559
06/2025
DOI: 10.1016/j.lfs.2025.123559
PMCID: PMC12094266
PMID: 40086745
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 a more 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 the 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 plays a protective role against bone loss by keeping the IL-17-neutrophil axis in check and directly inhibiting osteoclast formation in periodontitis.
Details
- Title: Subtitle
- Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis
- Creators
- Jinmei Zhang - University of IowaQiong Ding - University of IowaAngela X Wang - University of IowaMaoxuan Lin - Harvard UniversityNing Yu - The Forsyth Institute, Cambridge, MA, USAKevin Moss - East Carolina UniversityMegumi A WilliamsonDi Miao - University of IowaJulie T Marchesan - University of North Carolina at Chapel HillErliang Zeng - University of IowaWei Shi - University of IowaHongli Sun - University of IowaYu Leo Lei - The University of Texas MD Anderson Cancer CenterShaoping Zhang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Life sciences (1973), Vol.371, 123559
- DOI
- 10.1016/j.lfs.2025.123559
- PMID
- 40086745
- PMCID
- PMC12094266
- NLM abbreviation
- Life Sci
- ISSN
- 0024-3205
- eISSN
- 1879-0631
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Grant note
- National Human Genome Research Institute: 01100012C, R01HL087641, R01HL59367, R01HL086694 National Institutes of Health: U01HG004402 National Institute of Environmental Health Sciences: HHSN268200625226C National Institute of Dental and Craniofacial Research: P30ES010126 NIH: R01DE11551, R01DE021418 Colgate Award for Research Excellence (CARE): R01 DE032307, R01 DE026728, R01 DE030691, R01 DE032830
The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820110000 9C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C) , R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; National Institutes of Health contract HHSN268200625226C; National Institute of Environmental Health Sciences grant P30ES010126; and National Institute of Dental and Craniofacial Research grants R01DE11551, R01DE021418. This research was also funded by NIH grants R01 DE032307 (S.Z.) , R01 DE026728 and R01 DE030691 (Y.L. L.) , and R01 DE032830 (J.T.M) . This study was also partially supported by a Colgate Award for Research Excellence (CARE) (S.Z) .
- Language
- English
- Electronic publication date
- 03/12/2025
- Date published
- 06/2025
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery; Dental Research; Periodontics
- Record Identifier
- 9984799686502771
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