Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.

Crohn Disease / pathology Humans Epithelial Cells / metabolism Colon / pathology Ileum / pathology Lipocalin-2 / metabolism Dual Oxidases / genetics Male Nitric Oxide Synthase Type II / metabolism Female Adult Tumor Necrosis Factor-alpha / metabolism Intestinal Mucosa / pathology Middle Aged

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
22 Aug 2024

Historique:

received: 28 08 2023

accepted: 13 08 2024

medline: 22 8 2024

pubmed: 22 8 2024

entrez: 21 8 2024

Statut: epublish

Résumé

Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.

Identifiants

DOI: 10.1038/s41467-024-51580-7 PMID: 39169060

pubmed: 39169060

doi: 10.1038/s41467-024-51580-7

pii: 10.1038/s41467-024-51580-7

doi:

Substances chimiques

Lipocalin-2 0

Dual Oxidases EC 1.11.1.-

NOS2 protein, human EC 1.14.13.39

LCN2 protein, human 0

Nitric Oxide Synthase Type II EC 1.14.13.39

DUOX2 protein, human EC 1.6.3.1

Tumor Necrosis Factor-alpha 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

7204

Subventions

Organisme : Leona M. and Harry B. Helmsley Charitable Trust (Helmsley Charitable Trust)

ID : G-1903-03793

Informations de copyright

Références

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