期刊
CELL
卷 178, 期 6, 页码 1493-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.08.008
关键词
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资金
- Prix pour les jeunes chercheurs'' de la Fondation Bettencourt-Schueller
- Philippe Foundation
- Crohn's and Colitis Foundation
- NIH K23 Career Development Award [K23KD111995-01A1]
- Sanford J. Grossman Charitable Trust
- Boehringer Ingelheim Pharmaceuticals
- [U01 DK062429]
- [U01 DK062422]
- [R01 DK106593]
- [R56AI137244]
- [U24 AI118644]
- [U19 AI128949]
- [S10 OD023547-01]
Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.
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