A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease.

Journal

Nature immunology

ISSN: 1529-2916

Titre abrégé: Nat Immunol

Pays: United States

ID NLM: 100941354

Informations de publication

Date de publication:
22 Oct 2024

Historique:

received: 27 06 2023

accepted: 18 09 2024

medline: 23 10 2024

pubmed: 23 10 2024

entrez: 22 10 2024

Statut: aheadofprint

Résumé

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.

Identifiants

DOI: 10.1038/s41590-024-01994-8 PMID: 39438660

pubmed: 39438660

doi: 10.1038/s41590-024-01994-8

pii: 10.1038/s41590-024-01994-8

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

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