Nature Communications (Aug 2024)
Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn’s disease
- Jia Li,
- Alan J. Simmons,
- Caroline V. Hawkins,
- Sophie Chiron,
- Marisol A. Ramirez-Solano,
- Naila Tasneem,
- Harsimran Kaur,
- Yanwen Xu,
- Frank Revetta,
- Paige N. Vega,
- Shunxing Bao,
- Can Cui,
- Regina N. Tyree,
- Larry W. Raber,
- Anna N. Conner,
- Jennifer M. Pilat,
- Justin Jacobse,
- Kara M. McNamara,
- Margaret M. Allaman,
- Gabriella A. Raffa,
- Alain P. Gobert,
- Mohammad Asim,
- Jeremy A. Goettel,
- Yash A. Choksi,
- Dawn B. Beaulieu,
- Robin L. Dalal,
- Sara N. Horst,
- Baldeep S. Pabla,
- Yuankai Huo,
- Bennett A. Landman,
- Joseph T. Roland,
- Elizabeth A. Scoville,
- David A. Schwartz,
- M. Kay Washington,
- Yu Shyr,
- Keith T. Wilson,
- Lori A. Coburn,
- Ken S. Lau,
- Qi Liu
Affiliations
- Jia Li
- Center for Quantitative Sciences, Vanderbilt University Medical Center
- Alan J. Simmons
- Epithelial Biology Center, Vanderbilt University Medical Center
- Caroline V. Hawkins
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Sophie Chiron
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Marisol A. Ramirez-Solano
- Center for Quantitative Sciences, Vanderbilt University Medical Center
- Naila Tasneem
- Epithelial Biology Center, Vanderbilt University Medical Center
- Harsimran Kaur
- Epithelial Biology Center, Vanderbilt University Medical Center
- Yanwen Xu
- Epithelial Biology Center, Vanderbilt University Medical Center
- Frank Revetta
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center
- Paige N. Vega
- Epithelial Biology Center, Vanderbilt University Medical Center
- Shunxing Bao
- Department of Electrical and Computer Engineering, Vanderbilt University
- Can Cui
- Department of Computer Science, Vanderbilt University
- Regina N. Tyree
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Larry W. Raber
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Anna N. Conner
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Jennifer M. Pilat
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Justin Jacobse
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Kara M. McNamara
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Margaret M. Allaman
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Gabriella A. Raffa
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Alain P. Gobert
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Mohammad Asim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Jeremy A. Goettel
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Yash A. Choksi
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Dawn B. Beaulieu
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Robin L. Dalal
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Sara N. Horst
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Baldeep S. Pabla
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Yuankai Huo
- Department of Electrical and Computer Engineering, Vanderbilt University
- Bennett A. Landman
- Department of Electrical and Computer Engineering, Vanderbilt University
- Joseph T. Roland
- Epithelial Biology Center, Vanderbilt University Medical Center
- Elizabeth A. Scoville
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- David A. Schwartz
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- M. Kay Washington
- Program in Chemical and Physical Biology, Vanderbilt University School of Medicine
- Yu Shyr
- Center for Quantitative Sciences, Vanderbilt University Medical Center
- Keith T. Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Lori A. Coburn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center
- Ken S. Lau
- Center for Quantitative Sciences, Vanderbilt University Medical Center
- Qi Liu
- Center for Quantitative Sciences, Vanderbilt University Medical Center
- DOI
- https://doi.org/10.1038/s41467-024-51580-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 19
Abstract
Abstract 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.
