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

Autor: Li J; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Simmons AJ; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Hawkins CV; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Chiron S; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Ramirez-Solano MA; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Tasneem N; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Kaur H; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Xu Y; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Revetta F; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Vega PN; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Bao S; Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA., Cui C; Department of Computer Science, Vanderbilt University, Nashville, TN, USA., Tyree RN; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Raber LW; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Conner AN; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Pilat JM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Jacobse J; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., McNamara KM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Allaman MM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Raffa GA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Gobert AP; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Asim M; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Goettel JA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Choksi YA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA., Beaulieu DB; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Dalal RL; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Horst SN; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Pabla BS; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Huo Y; Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.; Department of Computer Science, Vanderbilt University, Nashville, TN, USA., Landman BA; Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.; Department of Computer Science, Vanderbilt University, Nashville, TN, USA., Roland JT; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Scoville EA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Schwartz DA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Washington MK; Program in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Shyr Y; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Wilson KT; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA. keith.wilson@vumc.org.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA. keith.wilson@vumc.org., Coburn LA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. lori.coburn@vumc.org.; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA. lori.coburn@vumc.org.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA. lori.coburn@vumc.org.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA. lori.coburn@vumc.org., Lau KS; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. ken.s.lau@vanderbilt.edu.; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA. ken.s.lau@vanderbilt.edu.; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA. ken.s.lau@vanderbilt.edu.; Program in Chemical and Physical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA. ken.s.lau@vanderbilt.edu.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA. ken.s.lau@vanderbilt.edu.; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. ken.s.lau@vanderbilt.edu., Liu Q; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. qi.liu@vumc.org.; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA. qi.liu@vumc.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 22; Vol. 15 (1), pp. 7204. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1038/s41467-024-51580-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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