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Updated: Jul 12, 2025
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Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
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A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease
Jia Li1,2, Alan J Simmons3,4, Sophie Chiron5
1Center for Quantitative Sciences, Vanderbilt Univerity Medical Center, Nashville, TN, USA.
Biorxiv : the Preprint Server for Biology
|October 24, 2023
Summary
Researchers discovered a new epithelial cell type, LND cells, significantly expanded in active Crohn's disease (CD). These cells play a role in CD immunopathogenesis and may serve as biomarkers for disease activity and treatment response.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Crohn's disease (CD) is a heterogeneous inflammatory disorder with immune dysregulation.
- Understanding cellular heterogeneity is crucial for characterizing CD pathogenesis.
Approach:
- Single-cell transcriptomics of 170 samples from 65 CD patients and 18 controls.
- Analysis of 202,359 cells from terminal ileum and ascending colon.
- In-situ RNA imaging and multiplexed protein imaging validated findings.
Key Points:
- Identified a novel epithelial cell type, LND cells, highly expressing LCN2, NOS2, and DUOX2.
- LND cells are rare in controls but expanded in active CD, enriched in antimicrobial and immunoregulation genes.
- LND cell abundance correlates with immune infiltration and CD susceptibility gene expression, indicating a role in pathogenesis.
- Two LND subpopulations (early and late) were identified, with their ratio linked to anti-TNF treatment response.
Conclusions:
- LND cells are pathogenic in both ileitis and colitis, highlighting their role in Crohn's disease.
- LND cells represent novel biomarkers for CD activity and predicting treatment response.
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