Mucosal Inflammation Shapes Human Neutrophil States in Tissue and Circulation

Authors

Fraser, D., Theofilou, V. I., Greenwell-Wild, T., Brenchley, L., Kanasi, E., Wang, C., Moutsopoulos, N.

Abstract

The oral mucosa is a prototypical human barrier reliant on neutrophils for homeostasis, as both neutrophil deficiency and excessive activation are linked to immunopathology. Yet, whether neutrophils acquire tissue-specific states in health or disease remains unclear. We incorporated single-cell RNA sequencing, spectral flow cytometry, and spatial proteomics across tooth-associated oral mucosa (gingiva) and interconnected compartments of blood and oral cavity to define neutrophil tissue specification in healthy individuals and patients with periodontitis, a neutrophil-dominated inflammatory disease. In health, mucosal neutrophils adopt discrete immunoregulatory states despite constant microbial exposure and mechanical injury. Periodontitis disrupts these programs through infiltration of blood-like neutrophil subsets, increased transcriptional noise, and heightened effector activation. Strikingly, oral inflammation systemically imprints on circulating neutrophils, marked by the expansion of a Rho-GTPase regulatory program that is shared across diverse human inflammatory conditions. Together, these findings establish a framework for understanding how localized tissue inflammation affects both neutrophil plasticity at barrier surfaces and conditioning of systemic neutrophil states with broad implications for inflammatory disease pathogenesis.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 25 Mar 2026.

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