Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy.
Crohn’s disease
high-dimensional profiling
inflammatory bowel disease
molecular classification
single-cell RNA sequencing
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
05 09 2019
05 09 2019
Historique:
received:
05
12
2018
revised:
06
05
2019
accepted:
05
08
2019
pubmed:
3
9
2019
medline:
17
6
2020
entrez:
3
9
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31474370
pii: S0092-8674(19)30896-7
doi: 10.1016/j.cell.2019.08.008
pmc: PMC7060942
mid: NIHMS1557672
pii:
doi:
Substances chimiques
Cytokines
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1493-1508.e20Subventions
Organisme : NIAID NIH HHS
ID : U19 AI128949
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK062429
Pays : United States
Organisme : NIH HHS
ID : S10 OD023547
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA190400
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062429
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI137244
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062422
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA078207
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106593
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK111995
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118644
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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