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Single-cell analyses of Crohn's disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions (Intraepithelial lymphocyte)
Natalia Jaeger, Ramya Gamini, Marina Cella, Jorge L. Schettini, Mattia Bugatti, Shanrong Zhao, Charles V. Rosadini, Ekaterina Esaulova, Blanda Di Luccia, Baylee Kinnett, William Vermi, Maxim N. Artyomov, Thomas A. Wynn, Ramnik J. Xavier, Scott A. Jelinsky, Marco Colonna
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+<ce><b3><ce><b4>T cells expressing ROR<ce><b3>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 TH17 but decreased CD8+T, <ce><b3><ce><b4>T, 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 <ce><b3><ce><b4>T cells and altered spatial distribution of IEL and LP T cell subsets.