TRAF3IP2-IL-17 Axis Strengthens the Gingival Defense against Pathogens.

Autor: Zhang J; Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA.; Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA., Sun L; Department of Microbiology & Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Withanage MHH; Division of Biostatistics and Computational Biology, University of Iowa College of Dentistry, Iowa City, IA, USA., Ganesan SM; Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA.; Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA., Williamson MA; Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA.; Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA., Marchesan JT; Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Jiao Y; Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Teles FR; Department of Basic & Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA., Yu N; The Forsyth Institute, Cambridge, MA, USA., Liu Y; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Wu D; Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Moss KL; Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Mangalam AK; Department of Pathology, University of Iowa College of Medicine, Iowa City, IA, USA., Zeng E; Division of Biostatistics and Computational Biology, University of Iowa College of Dentistry, Iowa City, IA, USA., Lei YL; Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, Ann Harbor, MI, USA., Zhang S; Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA.; Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA.
Jazyk: angličtina
Zdroj: Journal of dental research [J Dent Res] 2023 Jan; Vol. 102 (1), pp. 103-115. Date of Electronic Publication: 2022 Oct 24.
DOI: 10.1177/00220345221123256
Abstrakt: 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.
Databáze: MEDLINE