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Mucosal Inflammation Shapes Human Neutrophil States in Tissue and Circulation
David Fraser1,2, Vasileios I Theofilou1, Teresa Greenwell-Wild1
1Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892.
Biorxiv : the Preprint Server for Biology
|April 29, 2026
Summary
Neutrophils in the oral mucosa adopt unique states. Periodontitis disrupts these states and affects circulating neutrophils, impacting inflammatory disease. This study defines neutrophil tissue specification in health and disease.
Area of Science:
- Immunology
- Cell Biology
- Oral Biology
Background:
- The oral mucosa relies on neutrophils for homeostasis.
- Neutrophil dysfunction is linked to oral immunopathology.
- Tissue-specific neutrophil states in health and disease are not well understood.
Purpose of the Study:
- To define neutrophil tissue specification in the oral mucosa.
- To investigate how periodontitis alters neutrophil states.
- To understand the systemic impact of oral inflammation on neutrophils.
Main Methods:
- Single-cell RNA sequencing
- Spectral flow cytometry
- Spatial proteomics
- Analysis of gingiva, blood, and oral cavity neutrophils
Main Results:
- Healthy oral mucosal neutrophils exhibit distinct immunoregulatory states.
- Periodontitis causes infiltration of blood-like neutrophils and heightened activation.
- Oral inflammation induces systemic changes in circulating neutrophils, involving Rho-GTPase regulation.
Conclusions:
- Neutrophils acquire tissue-specific states in the oral mucosa.
- Periodontitis disrupts these states and conditions systemic neutrophils.
- Findings provide a framework for understanding neutrophil plasticity in inflammatory diseases.
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