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

Li, Jia; Simmons, Alan J.; Hawkins, Caroline V.; Chiron, Sophie; Ramirez-Solano, Marisol A.; Tasneem, Naila; Kaur, Harsimran; Xu, Yanwen; Revetta, Frank; Vega, Paige N.; Bao, Shunxing; Cui, Can; Tyree, Regina N.; Raber, Larry W.; Conner, Anna N.; Pilat, Jennifer M.; Jacobse, Justin; McNamara, Kara M.; Allaman, Margaret M.; Raffa, Gabriella A.; Gobert, Alain P.; Asim, Mohammad; Goettel, Jeremy A.; Choksi, Yash A.; Beaulieu, Dawn B.; Dalal, Robin L.; Horst, Sara N.; Pabla, Baldeep S.; Huo, Yuankai; Landman, Bennett A.; Roland, Joseph T.; Scoville, Elizabeth A.; Schwartz, David A.; Washington, M. Kay; Shyr, Yu; Wilson, Keith T.; Coburn, Lori A.; Lau, Ken S.; Liu, Qi

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 () and Qi Liu ()
Additional contact information
Jia Li: Vanderbilt University Medical Center
Alan J. Simmons: Vanderbilt University Medical Center
Caroline V. Hawkins: Vanderbilt University Medical Center
Sophie Chiron: Vanderbilt University Medical Center
Marisol A. Ramirez-Solano: Vanderbilt University Medical Center
Naila Tasneem: Vanderbilt University Medical Center
Harsimran Kaur: Vanderbilt University Medical Center
Yanwen Xu: Vanderbilt University Medical Center
Frank Revetta: Vanderbilt University Medical Center
Paige N. Vega: Vanderbilt University Medical Center
Shunxing Bao: Vanderbilt University
Can Cui: Vanderbilt University
Regina N. Tyree: Vanderbilt University Medical Center
Larry W. Raber: Vanderbilt University Medical Center
Anna N. Conner: Vanderbilt University Medical Center
Jennifer M. Pilat: Vanderbilt University Medical Center
Justin Jacobse: Vanderbilt University Medical Center
Kara M. McNamara: Vanderbilt University Medical Center
Margaret M. Allaman: Vanderbilt University Medical Center
Gabriella A. Raffa: Vanderbilt University Medical Center
Alain P. Gobert: Vanderbilt University Medical Center
Mohammad Asim: Vanderbilt University Medical Center
Jeremy A. Goettel: Vanderbilt University Medical Center
Yash A. Choksi: Vanderbilt University Medical Center
Dawn B. Beaulieu: Vanderbilt University Medical Center
Robin L. Dalal: Vanderbilt University Medical Center
Sara N. Horst: Vanderbilt University Medical Center
Baldeep S. Pabla: Vanderbilt University Medical Center
Yuankai Huo: Vanderbilt University
Bennett A. Landman: Vanderbilt University
Joseph T. Roland: Vanderbilt University Medical Center
Elizabeth A. Scoville: Vanderbilt University Medical Center
David A. Schwartz: Vanderbilt University Medical Center
M. Kay Washington: Vanderbilt University School of Medicine
Yu Shyr: Vanderbilt University Medical Center
Keith T. Wilson: Vanderbilt University Medical Center
Lori A. Coburn: Vanderbilt University Medical Center
Ken S. Lau: Vanderbilt University Medical Center
Qi Liu: Vanderbilt University Medical Center

Nature Communications, 2024, vol. 15, issue 1, 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.

Date: 2024
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DOI: 10.1038/s41467-024-51580-7

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