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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.<\/jats:p>","DOI":"10.64898\/2026.03.21.713286","type":"posted-content","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:50:11Z","timestamp":1774381811000},"source":"Crossref","is-referenced-by-count":0,"title":["Mucosal Inflammation Shapes Human Neutrophil States in Tissue and Circulation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-2503","authenticated-orcid":false,"given":"David","family":"Fraser","sequence":"first","affiliation":[{"name":"Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"},{"name":"National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios I.","family":"Theofilou","sequence":"additional","affiliation":[{"name":"Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Greenwell-Wild","sequence":"additional","affiliation":[{"name":"Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Brenchley","sequence":"additional","affiliation":[{"name":"Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"},{"name":"National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Kanasi","sequence":"additional","affiliation":[{"name":"Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki M.","family":"Moutsopoulos","sequence":"additional","affiliation":[{"name":"Human Barrier Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892"},{"name":"National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032622202528000_2026.03.21.713286v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.06.006"},{"key":"2026032622202528000_2026.03.21.713286v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3024"},{"key":"2026032622202528000_2026.03.21.713286v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.05.004"},{"key":"2026032622202528000_2026.03.21.713286v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.04.013"},{"key":"2026032622202528000_2026.03.21.713286v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2921"},{"key":"2026032622202528000_2026.03.21.713286v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.05.001"},{"key":"2026032622202528000_2026.03.21.713286v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-02402006-5"},{"key":"2026032622202528000_2026.03.21.713286v1.8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-688887"},{"key":"2026032622202528000_2026.03.21.713286v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.003"},{"key":"2026032622202528000_2026.03.21.713286v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22973-9"},{"key":"2026032622202528000_2026.03.21.713286v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.01.002"},{"key":"2026032622202528000_2026.03.21.713286v1.12","doi-asserted-by":"crossref","unstructured":"Ng MSF , Kwok I , Tan L , Shi C , Cerezo-Wallis D , Tan Y , et al. 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