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Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
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Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
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Journal Article
Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
2021
Overview
Crohn’s disease (CD) is a chronic transmural inflammation of intestinal segments caused by dysregulated interaction between microbiome and gut immune system. Here, we profile, via multiple single-cell technologies, T cells purified from the intestinal epithelium and lamina propria (LP) from terminal ileum resections of adult severe CD cases. We find that intraepithelial lymphocytes (IEL) contain several unique T cell subsets, including NKp30
+
γδT cells expressing RORγt and producing IL-26 upon NKp30 engagement. Further analyses comparing tissues from non-inflamed and inflamed regions of patients with CD versus healthy controls show increased activated T
H
17 but decreased CD8
+
T, γδT, T
FH
and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8
+
, as well as reduced CD4
+
T cells with an elevated T
H
17 over Treg/T
FH
ratio. Our analyses of CD tissues thus suggest a potential link, pending additional validations, between transmural inflammation, reduced IEL γδT cells and altered spatial distribution of IEL and LP T cell subsets.
Crohn’s disease results from transmural inflammation in the gut, but analyses of local immune populations are still lacking. Here, the authors show, by combining multiple single-cell approaches, that intraepithelial and lamina propria T cells are heterogenous, show unique phenotypes, and exhibit altered subsets upon inflammation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/21
/ 13/31
/ 13/51
/ 45/91
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - metabolism
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Gene Expression Profiling - methods
/ Humanities and Social Sciences
/ Humans
/ Ileum
/ Intraepithelial Lymphocytes - immunology
/ Intraepithelial Lymphocytes - metabolism
/ Science
/ Single-Cell Analysis - methods
/ T-Lymphocyte Subsets - immunology
/ T-Lymphocyte Subsets - metabolism
/ T-Lymphocytes, Regulatory - immunology
