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. (2024). Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn disease. Nature Communications, 15(1), 7204.
This study investigates Crohn’s disease (CD), a chronic inflammatory condition affecting both the gastrointestinal system and other parts of the body due to immune system dysregulation. By analyzing over 202,000 cells from 170 tissue samples across 83 patients, the researchers identified a specific epithelial cell type, termed 鈥楲ND,鈥� present in both the terminal ileum and ascending colon. These LND cells, which show high expression of genes related to antimicrobial response and immune regulation (such as LCN2, NOS2, and DUOX2), were found to be rare in individuals without inflammatory bowel disease (IBD) but significantly expanded in patients with active CD.
Further in-situ RNA and protein imaging confirmed the presence of LND cells, which interact closely with immune cells and express genes linked to CD susceptibility, suggesting their involvement in the disease immune dysfunction. Additionally, the study identified early and late subpopulations of LND cells, each with distinct developmental trajectories. Interestingly, patients with a higher ratio of late-to-early LND cells were more likely to respond positively to anti-TNF treatment, a common therapy for CD. These findings highlight a potentially pathogenic role for LND cells in CD and provide new insights into disease mechanisms and treatment responses.
A Schematic for processing endoscopic and surgical samples from TI and AC for
non-IBD controls, inactive and active CD patients. B Summary of the number of
samples in each group. C UMAP of 155,093 cells from endoscopy samples colored
by cell clusters. D Dotplot showing markers for each cell type. E UMAP of 155,093
cells colored by tissue origin, TI (brown) or AC (blue). F Proportion of each cell
cluster in TI (brown) and AC samples (blue). G UMAP of 155,093 cells colored by
disease status, controls (tan), inactive (green) or active CD (purple). H MDS plot of
cell compositional differences across all endoscopy specimens