Single-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis.

Humans Keratinocytes / metabolism Single-Cell Analysis Periodontitis / microbiology Cell Communication Cytokines / metabolism Periodontium / microbiology Immunity, Innate In Situ Hybridization, Fluorescence Male Metagenomics / methods Bacteria / metabolism Female Adult Adaptive Immunity

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
14 Jun 2024

Historique:

received: 26 08 2023

accepted: 20 05 2024

medline: 15 6 2024

pubmed: 15 6 2024

entrez: 14 6 2024

Statut: epublish

Résumé

Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.

Identifiants

DOI: 10.1038/s41467-024-49037-y PMID: 38876998

pubmed: 38876998

doi: 10.1038/s41467-024-49037-y

pii: 10.1038/s41467-024-49037-y

doi:

Substances chimiques

Cytokines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

5016

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)

ID : 1K99DE033428

Informations de copyright

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