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

Date:	22 August 2024
PMID:	PMC11339313
Category:	N/A
Authors:	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
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.

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Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center