Serum Amyloid A Regulates Th17 Response To Promote Periodontitis

This study aims to explore the relationship between SAA expression and Th17 immune response, and to investigate whether SAA contributes to periodontitis progression by regulating Th17 cell differentiation and function. SAA expression patterns and Th17 cell proportions were analyzed using single-cell transcriptomic data from gingival tissues of healthy individuals and periodontitis patients, with validation from public datasets and mIHC staining. Ligature-induced periodontitis was established in 8-week-old male C57BL/6J wild-type and Saa1/2 knockout (SAA⁻/⁻) mice. Wild-type mice received the SAA antagonist 5-MP, while SAA⁻/⁻ mice were treated with recombinant SAA1, both via local gingival injections. Periodontal inflammation and bone loss were assessed by micro-CT, H&E, and TRAP staining. SAA protein levels were measured by IHC and ELISA, and Th17 cell proportions by flow cytometry. RT-qPCR was used to quantify SAA1, SAA2, and Th17-related cytokine mRNA levels. This study was approved by the institutional ethics committee. Periodontitis is characterized by increased Th17 cell infiltration and elevated SAA expression—primarily from epithelial and fibroblast cells. As the disease progresses, SAA expression, Th17-related cytokines, and Th17 cell proportions increase, and decline with the resolution of periodontitis. Gingival SAA levels strongly correlate with IL-17⁺IFN-γ⁺Th17 cells. Blocking or deleting SAA alleviates periodontal inflammation and reduces Th17 responses, whereas SAA supplementation reverses these effects. SAA exacerbates periodontitis by modulating the Th17 response and may serve as a potential therapeutic target.