Single-cell analyses of Crohn's disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions

Nat Commun. 2021 Mar 26;12(1):1921. doi: 10.1038/s41467-021-22164-6.


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 TH17 but decreased CD8+T, γδT, TFH and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8+, as well as reduced CD4+T cells with an elevated TH17 over Treg/TFH 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Crohn Disease / immunology*
  • Crohn Disease / pathology
  • Gene Expression Profiling / methods
  • Humans
  • Intraepithelial Lymphocytes / immunology*
  • Intraepithelial Lymphocytes / metabolism
  • Lymphocyte Count
  • Single-Cell Analysis / methods*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism