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Single cell transcriptome atlas of immune cells in human small intestine and in celiac disease

Nader Atlasy, Anna Bujko, Peter B Brazda, Eva Janssen-Megens, Espen S. Bækkevold, Jørgen Jahnsen, Frode L. Jahnsen, View ORCID ProfileHendrik G. Stunnenberg
doi: https://doi.org/10.1101/721258
Nader Atlasy
1Department of Molecular Biology, Science Faculty, Radboud University, Nijmegen, The Netherlands
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Anna Bujko
2Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Peter B Brazda
1Department of Molecular Biology, Science Faculty, Radboud University, Nijmegen, The Netherlands
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Eva Janssen-Megens
1Department of Molecular Biology, Science Faculty, Radboud University, Nijmegen, The Netherlands
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Espen S. Bækkevold
2Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Jørgen Jahnsen
3Department of Gastroenterology, Akershus University Hospital and University of Oslo, Oslo, Norway
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Frode L. Jahnsen
2Department of Pathology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Hendrik G. Stunnenberg
1Department of Molecular Biology, Science Faculty, Radboud University, Nijmegen, The Netherlands
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  • ORCID record for Hendrik G. Stunnenberg
  • For correspondence: h.stunnenberg@ncmls.ru.nl
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Abstract

Celiac disease (CeD) is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine1,2. The CeD lesion is characterized by crypt hyperplasia, villous atrophy and chronic inflammation with accumulation of leukocytes both in the lamina propria (LP) and in the epithelium3, which eventually leads to destruction of the intestinal epithelium1 and subsequent digestive complications and higher risk of non-hodgkin lymphoma4. A lifetime gluten-free diet is currently the only available treatment5. Gluten-specific LP CD4 T cells and cytotoxic intraepithelial CD8+ T cells are thought to be central in disease pathology1,6-8, however, CeD is a complex immune-mediated disorder and to date the findings are mostly based on analysis of heterogeneous cell populations and on animal models. Here, we comprehensively explore the cellular heterogeneity of CD45+ immune cells in human small intestine using index-sorting single-cell RNA-sequencing9,10. We find that myeloid and mast cell transcriptomes are reshaped in CeD. We observe extensive changes in the proportion and transcriptomes of CD4+ and CD8+ T cells and define a CD3zeta expressing NK-T-like cell population present in the control LP and epithelial layers that is absent and replaced in CeD. Our findings show that the immune landscape is dramatically changed in active CeD which provide new insights and considerably extend the current knowledge of CeD immunopathology.

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Posted August 01, 2019.
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Single cell transcriptome atlas of immune cells in human small intestine and in celiac disease
Nader Atlasy, Anna Bujko, Peter B Brazda, Eva Janssen-Megens, Espen S. Bækkevold, Jørgen Jahnsen, Frode L. Jahnsen, Hendrik G. Stunnenberg
bioRxiv 721258; doi: https://doi.org/10.1101/721258
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Single cell transcriptome atlas of immune cells in human small intestine and in celiac disease
Nader Atlasy, Anna Bujko, Peter B Brazda, Eva Janssen-Megens, Espen S. Bækkevold, Jørgen Jahnsen, Frode L. Jahnsen, Hendrik G. Stunnenberg
bioRxiv 721258; doi: https://doi.org/10.1101/721258

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