{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:40:33Z","timestamp":1778136033729,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Yu Leo Lei","award":["R01 DE026728"],"award-info":[{"award-number":["R01 DE026728"]}]},{"name":"Yu Leo Lei","award":["R01 DE030691"],"award-info":[{"award-number":["R01 DE030691"]}]},{"name":"Julie T Marchesan","award":["K01DE027087"],"award-info":[{"award-number":["K01DE027087"]}]},{"name":"Shaoping Zhang","award":["R00 DE027086"],"award-info":[{"award-number":["R00 DE027086"]}]},{"name":"Yizu Jiao","award":["F32 DE026688"],"award-info":[{"award-number":["F32 DE026688"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n                    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\u2013associated factor 3 interacting protein 2 ( TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)\u201317 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\u2013mediated 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\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis\u2013induced 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\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    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\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    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\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1177\/00220345221123256","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T01:00:34Z","timestamp":1666659634000},"page":"103-115","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["TRAF3IP2\u2013IL-17 Axis Strengthens the Gingival Defense against Pathogens"],"prefix":"10.1177","volume":"102","author":[{"given":"J.","family":"Zhang","sequence":"first","affiliation":[{"name":"Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA"},{"name":"Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.H.H.","family":"Withanage","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Computational Biology, University of Iowa College of Dentistry, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.M.","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA"},{"name":"Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.A.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Iowa Institute of Oral Health Research, University of Iowa College of Dentistry, Iowa City, IA, USA"},{"name":"Periodontics, University of Iowa College of Dentistry, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-3193","authenticated-orcid":false,"given":"J.T.","family":"Marchesan","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.R.","family":"Teles","sequence":"additional","affiliation":[{"name":"Department of Basic & Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Yu","sequence":"additional","affiliation":[{"name":"The Forsyth Institute, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.L.","family":"Moss","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.K.","family":"Mangalam","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa College of Medicine, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Zeng","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Computational Biology, University of Iowa College of Dentistry, Iowa City, IA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.L.","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, Ann Harbor, MI, 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