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

Natalia Jaeger, Ramya Gamini, Marina Cella, Jorge L. Schettini, Mattia Bugatti, Shanrong Zhao, Charles V. Rosadini, Ekaterina Esaulova, Blanda Luccia, Baylee Kinnett, William Vermi, Maxim N. Artyomov, Thomas A. Wynn, Ramnik J. Xavier, Scott A. Jelinsky and Marco Colonna ()
Additional contact information
Natalia Jaeger: Washington University School of Medicine
Ramya Gamini: Pfizer Worldwide Research, Development and Medical
Marina Cella: Washington University School of Medicine
Jorge L. Schettini: Pfizer Worldwide Research, Development and Medical
Mattia Bugatti: University of Brescia
Shanrong Zhao: Pfizer Worldwide Research, Development and Medical
Charles V. Rosadini: Pfizer Worldwide Research, Development and Medical
Ekaterina Esaulova: Washington University School of Medicine
Blanda Luccia: Washington University School of Medicine
Baylee Kinnett: Washington University School of Medicine
William Vermi: University of Brescia
Maxim N. Artyomov: Washington University School of Medicine
Thomas A. Wynn: Pfizer Worldwide Research, Development and Medical
Ramnik J. Xavier: Immunology Program, Infectious Disease and Microbiome Program, Broad Institute of MIT
Scott A. Jelinsky: Pfizer Worldwide Research, Development and Medical
Marco Colonna: Washington University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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+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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22164-6

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DOI: 10.1038/s41467-021-22164-6

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