IADR Abstract Archives
TRAF3IP2-Mediated IL-17 Pathway Enhances Gingival Defense in Periodontitis
Objectives: Through a genome-wide association study, we identified a periodontitis-associated risk alelle within the TRAF3IP2 locus. The role of TRAF3IP2, the non-redundant IL-17 receptor adaptor, in periodontal disease remains to be investigated. The objective of this study is to assess the activity of TRAF3IP2-mediated IL-17 pathway in a periodontal pathogen, Porphyromonas gingivalis (P.g), induced periodontitis model.
Methods: Traf3ip2 knockout (Traf3ip2-/-) and wild type (WT) control mice were orally gavaged with P.g A7436 strain or vehicle carrier carboxymethylcellulose according to an established protocol. Alveolar bone levels were compared between Traf3ip2-/-and WT mice through microCT. P.g in oral gingiva was quantified by realtime-qPCR. Neutrophils in gingiva were stained by immunohistochemistry with a neutrophil-specific marker (Ly6G). Microbial communities in the Traf3ip2-/- and WT oral plaque were analyzed through 16s rRNA sequencing. NanoString was used to analyze the mouse gingival transcriptome profile. The ligature-promoted bacterial invasion in gingiva under P.g challenge was compared in Traf3ip2-/- to WT mice through direct culture plating.
Results: The net bone loss between P.g. and carboxymethylcellulose challenge in Traf3ip2-/- mice was significantly more than that of WT controls (p<0.01). Neutrophils were significantly less present in the KO than WT gingiva (p<0.01). P.g. was significantly higher in KO oral plaque than WT samples (p<0.001). We observed a distinct microbial profile in the Traf3ip2-/- mouse plaque . While significantly more Corynebacterium and Staphylococcus were associated with WT mouse oral plaque, Streptococcus was almost exclusively present in the Traf3ip2-/- plaque at any given time point in the gavage model. A lower transcriptional expression of epithelial homeostasis and barrier defense-associated genes was identified in Traf3ip2-/- mouse gingiva. In addition, significantly more live bacteria invaded in Traf3ip2-/- than WT gingiva under both aerobic and anaerobic conditions.
Conclusions: TRAF3IP2-mediated homeostatic IL-17 plays an essential role in P.g induced periodontitis through enhancing mucosal barrier defense.
Methods: Traf3ip2 knockout (Traf3ip2-/-) and wild type (WT) control mice were orally gavaged with P.g A7436 strain or vehicle carrier carboxymethylcellulose according to an established protocol. Alveolar bone levels were compared between Traf3ip2-/-and WT mice through microCT. P.g in oral gingiva was quantified by realtime-qPCR. Neutrophils in gingiva were stained by immunohistochemistry with a neutrophil-specific marker (Ly6G). Microbial communities in the Traf3ip2-/- and WT oral plaque were analyzed through 16s rRNA sequencing. NanoString was used to analyze the mouse gingival transcriptome profile. The ligature-promoted bacterial invasion in gingiva under P.g challenge was compared in Traf3ip2-/- to WT mice through direct culture plating.
Results: The net bone loss between P.g. and carboxymethylcellulose challenge in Traf3ip2-/- mice was significantly more than that of WT controls (p<0.01). Neutrophils were significantly less present in the KO than WT gingiva (p<0.01). P.g. was significantly higher in KO oral plaque than WT samples (p<0.001). We observed a distinct microbial profile in the Traf3ip2-/- mouse plaque . While significantly more Corynebacterium and Staphylococcus were associated with WT mouse oral plaque, Streptococcus was almost exclusively present in the Traf3ip2-/- plaque at any given time point in the gavage model. A lower transcriptional expression of epithelial homeostasis and barrier defense-associated genes was identified in Traf3ip2-/- mouse gingiva. In addition, significantly more live bacteria invaded in Traf3ip2-/- than WT gingiva under both aerobic and anaerobic conditions.
Conclusions: TRAF3IP2-mediated homeostatic IL-17 plays an essential role in P.g induced periodontitis through enhancing mucosal barrier defense.