Neutrophil heterogeneity under IL-17A deficiency in experimental periodontitis
- 1Division of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong
- 2Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong
- 3Division of Periodontology and Implant Dentistry, Faculty of Dentistry, The University of Hong Kong
Abstract
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.
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BibTeX
@article{tang2026neutrophil,
title = {{Neutrophil heterogeneity under IL-17A deficiency in experimental periodontitis}},
author = {Zhongyuan Tang and Renjie Hu and Luying Zhu and Jing Hu and Fan Xiao and Lijian Jin and Liwei Lu and Yanqi Yang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1963694},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963694/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neutrophil heterogeneity under IL-17A deficiency in experimental periodontitis
AU - Zhongyuan Tang
AU - Renjie Hu
AU - Luying Zhu
AU - Jing Hu
AU - Fan Xiao
AU - Lijian Jin
AU - Liwei Lu
AU - Yanqi Yang
PY - 2026
DA - 2026/10/13
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1963694
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963694/full
AB - 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.
SN - 1664-3224
ER -