Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis.

Autor: Iwasaki N; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Poposki JA; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Kidoguchi M; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Oka A; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Klingler AI; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Stevens WW; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Suh LA; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Bai J; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Peters AT; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Grammer LC; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Welch KC; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Smith SS; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Conley DB; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Bochner BS; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill., Schleimer RP; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Kern RC; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Tan BK; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill., Kato A; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: a-kato@northwestern.edu.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2024 Nov 09. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1016/j.jaci.2024.10.032
Abstrakt: Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NP) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear.
Objective: To reveal the roles and heterogeneity of neutrophils in NP tissue by single-cell RNA sequencing analysis.
Methods: We developed a novel microwell-based single-cell RNA sequencing assay using granulocyte-enriched samples from 5 control sinus tissues, 5 NP tissues and patient-matched peripheral blood (PB) samples. This approach allowed for examination of differential expression of genes in NP neutrophils by the Benjamini-Hochberg algorithm and predicted the overall function of NP neutrophils by pathway and Gene Ontology enrichment analyses.
Results: After performing all quality control steps, we successfully detected neutrophils. We identified 333 downregulated and 128 upregulated genes in NP neutrophils (1,151 cells) compared with all PB neutrophils (13,591 cells) (>1.5-fold, q < 0.05) and found commonly dysregulated genes in NP neutrophils compared with both all PB and control sinus tissue neutrophils (3,136 cells). Commonly downregulated genes in NP neutrophils were associated with the innate immune system, and upregulated genes were associated with nuclear factor-κB signaling, cytokine activity, and cellular response to oxygen-containing compounds. NP neutrophils displayed 4 clusters revealing potential heterogeneity of neutrophils in NP tissue.
Conclusions: Elevated neutrophils in NP tissue appear to exist in several subphenotypes that may play important pathogenic roles in CRSwNP.
Competing Interests: Disclosure statement This research was supported in part by Regeneron Pharmaceuticals, National Institutes of Health grants (P01AI145818, R01AI137174, and U19AI136443) and by a grant from the Ernest S. Bazley Foundation. Disclosure of potential conflict of interest: W. W. Stevens served on advisory boards for GSK, Regeneron, and Melinta Therapeutics. A. T. Peters has served on advisory boards for Sanofi-Genzyme/Regeneron, OptiNose, AstraZeneca, Novartis, and GSK and has received research support from OptiNose and Sanofi/Regeneron. L. C. Grammer reports personal fees from Astellas Pharmaceuticals. K. C. Welch reports consultant fees from Baxter, OptiNose, and Acclarent. D. B. Conley reports consulting fees from Medtronic and Sanofi/Regeneron. R. P. Schleimer reports personal fees from Intersect ENT, Merck, GlaxoSmithKline, Sanofi, AstraZeneca/Medimmune, Genentech, ActoBio Therapeutics, Lyra Therapeutics, Astellas Pharma Inc., and Otsuka Inc and has royalty rights to Siglec-8 and Siglec-8–ligand related patents licensed by Johns Hopkins to Allakos Inc. R. C. Kern reports consulting fees from Lyra Therapeutics, Medtronic, GSK, Genentech, and Sanofi/Regeneron. B. S. Bochner received remuneration for serving on the scientific advisory board of Allakos, Inc, and owns stock in Allakos; has served as a consultant for GSK, Third Harmonic Bio, Lupagen, Acelyrin, and Sanofi/Regeneron; receives publication-related royalty payments from Elsevier and UpToDate; and is a co-inventor on existing Siglec-8–related patents and thus may be entitled to a share of royalties received by Johns Hopkins University during development and potential sales of such products. B. S. Bochner is also a cofounder of Allakos, which makes him subject to certain restrictions under university policy; the terms of this arrangement are being managed by Johns Hopkins University and Northwestern University in accordance with their conflict-of-interest policies. B. K. Tan reports personal fees from Sanofi Regeneron/Genzyme and GSK. A. Kato has served on an advisory board for AstraZeneca, reports a gift for his research from Lyra Therapeutics, and has received research grants from Regeneron and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest.
(Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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