Single-cell analyses of Crohn's disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33771991.
- Also identified by DOI 10.1038/s41467-021-22164-6 and PMC identifier 7997960.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>+</sup>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<sub>H</sub>17 but decreased CD8<sup>+</sup>T, γδT, T<sub>FH</sub> and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8<sup>+</sup>, as well as reduced CD4<sup>+</sup>T cells with an elevated T<sub>H</sub>17 over Treg/T<sub>FH</sub> 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.
Medical subject headings
- Crohn Disease
- Intraepithelial Lymphocytes
- Single-Cell Analysis
- T-Lymphocyte Subsets