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

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(+)gamma delta T cells expressing ROR gamma t 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, gamma delta T, 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 gamma delta T 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.

Automated summary

Crohn's disease is a chronic transmural inflammation in the gut caused by dysregulated interaction between microbiome and gut immune system. Studies have shown that T cells from intestinal epithelium and lamina propria in CD patients exhibit unique subsets and altered phenotypes during inflammation.