Journal article
TRAF3IP2–IL-17 Axis Strengthens the Gingival Defense against Pathogens
Journal of dental research, Vol.102(1), pp.103-115
01/2023
DOI: 10.1177/00220345221123256
PMCID: PMC9780753
PMID: 36281065
Abstract
Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting structures. One such genetic locus was the tumor necrosis factor receptor–associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)–17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17–mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2–/–) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis–induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2–/– mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2–/– mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2–/– mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2–/– mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.
Details
- Title: Subtitle
- TRAF3IP2–IL-17 Axis Strengthens the Gingival Defense against Pathogens
- Creators
- L. Sun - University of North Carolina at Chapel HillM.H.H. Withanage - University of IowaS.M. Ganesan - University of IowaM.A. Williamson - University of IowaJ.T. Marchesan - University of North Carolina at Chapel HillY. Jiao - University of North Carolina at Chapel HillF.R. Teles - University of PennsylvaniaN. Yu - The Forsyth InstituteY. Liu - University of North Carolina at Chapel HillD. Wu - University of North Carolina at Chapel HillK.L. Moss - University of North Carolina at Chapel HillA.K. Mangalam - University of IowaE. Zeng - University of IowaY.L. Lei - University of Michigan–Ann ArborS. Zhang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of dental research, Vol.102(1), pp.103-115
- DOI
- 10.1177/00220345221123256
- PMID
- 36281065
- PMCID
- PMC9780753
- NLM abbreviation
- J Dent Res
- ISSN
- 0022-0345
- eISSN
- 1544-0591
- Publisher
- SAGE Publications
- Grant note
- F32 DE026688 / Yizu Jiao K01DE027087 / Julie T Marchesan R01 DE026728 / Yu Leo Lei R00 DE027086 / Shaoping Zhang R01 DE030691 / Yu Leo Lei
- Language
- English
- Electronic publication date
- 10/24/2022
- Date published
- 01/2023
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Pathology; Iowa Neuroscience Institute; Biostatistics; Dental Research; Periodontics
- Record Identifier
- 9984306743202771
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