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Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease

Author

Listed:
  • Nader Atlasy

    (Radboud University)

  • Anna Bujko

    (University of Oslo and Oslo University Hospital, Rikshospitalet
    Ghent University)

  • Espen S. Bækkevold

    (University of Oslo and Oslo University Hospital, Rikshospitalet)

  • Peter Brazda

    (Radboud University
    Princess Maxima Centre for Pediatric Oncology)

  • Eva Janssen-Megens

    (Radboud University
    NimaGen B.V.)

  • Knut E. A. Lundin

    (University of Oslo
    University of Oslo
    Oslo University Hospital Rikshospitalet)

  • Jørgen Jahnsen

    (Akershus University Hospital and University of Oslo)

  • Frode L. Jahnsen

    (University of Oslo and Oslo University Hospital, Rikshospitalet)

  • Hendrik G. Stunnenberg

    (Radboud University
    Princess Maxima Centre for Pediatric Oncology)

Abstract

Celiac disease is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine leading to destruction of the lining epithelium. Current treatment focusses on lifelong adherence to a gluten-free diet. Gluten-specific CD4+ T cells and cytotoxic intraepithelial CD8+ T cells have been proposed to be central in disease pathogenesis. Here we use unbiased single-cell RNA-sequencing and explore the heterogeneity of CD45+ immune cells in the human small intestine. We show altered myeloid cell transcriptomes present in active celiac lesions. CD4+ and CD8+ T cells transcriptomes show extensive changes and we define a natural intraepithelial lymphocyte population that is reduced in celiac disease. We show that the immune landscape in Celiac patients on a gluten-free diet is only partially restored compared to control samples. Altogether, we provide a single cell transcriptomic resource that can inform the immune landscape of the small intestine during Celiac disease.

Suggested Citation

  • Nader Atlasy & Anna Bujko & Espen S. Bækkevold & Peter Brazda & Eva Janssen-Megens & Knut E. A. Lundin & Jørgen Jahnsen & Frode L. Jahnsen & Hendrik G. Stunnenberg, 2022. "Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32691-5
    DOI: 10.1038/s41467-022-32691-5
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    References listed on IDEAS

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    1. Peter A. Szabo & Hanna Mendes Levitin & Michelle Miron & Mark E. Snyder & Takashi Senda & Jinzhou Yuan & Yim Ling Cheng & Erin C. Bush & Pranay Dogra & Puspa Thapa & Donna L. Farber & Peter A. Sims, 2019. "Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    2. Kim-Long Truong & Stephan Schlickeiser & Katrin Vogt & David Boës & Katarina Stanko & Christine Appelt & Mathias Streitz & Gerald Grütz & Nadja Stobutzki & Christian Meisel & Christina Iwert & Stefan , 2019. "Killer-like receptors and GPR56 progressive expression defines cytokine production of human CD4+ memory T cells," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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