Neutrophil heterogeneity under IL-17A deficiency in experimental periodontitis

Periodontitis is a dysbiotic inflammatory disease characterized by progressive periodontal destruction, in which neutrophils play a central but functionally diverse role. IL-17A is closely linked to neutrophil-mediated host responses; however, how IL-17A deficiency reshapes neutrophil heterogeneity during periodontitis remains unclear. Here, we established a Porphyromonas gingivalis-induced experimental periodontitis model in wild-type and IL-17A knockout mice and integrated micro-CT, histology, 16S rRNA sequencing, and single-cell RNA sequencing to define the consequences of IL-17A loss in the periodontal microenvironment. IL-17A deficiency exacerbated alveolar bone loss and osteoclast accumulation and was associated with altered oral microbial composition consistent with dysbiosis. Single-cell profiling revealed marked remodeling of the immune landscape, with impaired neutrophil accumulation and altered neutrophil subset composition in IL-17A-deficient periodontal tissues. Neutrophils from IL-17A knockout mice showed reduced inflammatory chemokine/cytokine programs and a shift toward antimicrobial granule-associated, extracellular matrix-responsive, and TGF-β/THBS-linked transcriptional states. Trajectory, transcriptional regulatory, and cell-cell communication analyses further demonstrated that IL-17A deficiency disrupted neutrophil state transitions and attenuated neutrophil-centered CCL, CXCL, TNF, SELPG, and ICAM signaling while enhancing matrix-associated communication pathways. Together, these findings identify IL-17A deficiency as a driver of neutrophil reprogramming and aggravated periodontal destruction and indicate an association with microbial dysbiosis, providing single-cell-level insight into the IL-17A-neutrophil axis in dysbiotic periodontitis.