Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses.
Sci Immunol
; 5(50)2020 08 21.
Article
in En
| MEDLINE
| ID: mdl-32826341
ABSTRACT
Inflammatory bowel disease (IBD) encompasses a spectrum of gastrointestinal disorders driven by dysregulated immune responses against gut microbiota. We integrated single-cell RNA and antigen receptor sequencing to elucidate key components, cellular states, and clonal relationships of the peripheral and gastrointestinal mucosal immune systems in health and ulcerative colitis (UC). UC was associated with an increase in IgG1+ plasma cells in colonic tissue, increased colonic regulatory T cells characterized by elevated expression of the transcription factor ZEB2, and an enrichment of a γδ T cell subset in the peripheral blood. Moreover, we observed heterogeneity in CD8+ tissue-resident memory T (TRM) cells in colonic tissue, with four transcriptionally distinct states of differentiation observed across health and disease. In the setting of UC, there was a marked shift of clonally related CD8+ TRM cells toward an inflammatory state, mediated, in part, by increased expression of the T-box transcription factor Eomesodermin. Together, these results provide a detailed atlas of transcriptional changes occurring in adaptive immune cells in the context of UC and suggest a role for CD8+ TRM cells in IBD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colitis, Ulcerative
/
T-Lymphocytes, Regulatory
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Intraepithelial Lymphocytes
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Memory T Cells
Limits:
Animals
/
Humans
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Male
Language:
En
Journal:
Sci Immunol
Year:
2020
Document type:
Article
Affiliation country:
Estados Unidos
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA