Regulation Of Tertiary Lymphoid Structure Formation In Periodontitis

This study investigates the role of gingival fibroblasts in the formation of tertiary lymphoid structures (TLSs) in periodontitis and their impact on inflammation. Periodontal tissues, clinical data were collected from patients with different stages of periodontitis (n = 44). Multiplex immunohistochemical staining and single-cell sequencing were used to assess the relationship between TLSs and periodontitis severity and surgical prognosis. Primary human gingival fibroblasts (HGFs) were isolated were isolated for in vitro experiments, including qPCR, ELISA, and Western blot, to examine the IFN I signaling axis's role in fibroblast activation. In vivo experiments were performed using a ligature-induced periodontitis (LIP) mouse model, and flow cytometry, immunofluorescence, immunohistochemistry staining was used to explain the effects of blocking IFNIAR1 in LIP mouse. Mature TLSs were found in stage III and IV periodontitis tissues, correlating with post-surgical progression. Single-cell sequencing highlighted the CXCL13-CXCR5 axis in TLSs formation, with Follicular helper T cells (Tfhs) and memory B cells as key rols. The IFN I signaling promotes the transformation of HGFs into lymphoid tissue fibroblasts. In vitro blockade of the IFN I signaling axis weakened CXCL13 production of HGFs. In vitro IFN I blockade reduced fibroblast secretion, while in vivo blockade decreased Tfh infiltration and non-switched memory B cell expansion, attenuating bone destruction. Severe periodontitis is associated with TLSs that negatively impact surgical outcomes. The IFN I axis drives TLSs formation via CXCL13-CXCR5, with Tfh cells promoting non-switched memory B cell expansion and RANKL secretion, exacerbating bone destruction.