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High-dimensional profiling reveals Tc17 cell enrichment in active Crohn’s disease and identifies a potentially targetable signature

Author

Listed:
  • A.-M. Globig

    (Faculty of Medicine, University Medical Center Freiburg)

  • A. V. Hipp

    (Faculty of Medicine, University Medical Center Freiburg)

  • P. Otto-Mora

    (Faculty of Medicine, University Medical Center Freiburg)

  • M. Heeg

    (Faculty of Medicine, University Medical Center Freiburg)

  • L. S. Mayer

    (Faculty of Medicine, University Medical Center Freiburg)

  • S. Ehl

    (Faculty of Medicine, University Medical Center Freiburg
    University of Freiburg
    German Cancer Consortium (DKTK))

  • H. Schwacha

    (Faculty of Medicine, University Medical Center Freiburg)

  • M. Bewtra

    (University of Pennsylvania Perelman School of Medicine)

  • V. Tomov

    (University of Pennsylvania Perelman School of Medicine)

  • R. Thimme

    (Faculty of Medicine, University Medical Center Freiburg)

  • P. Hasselblatt

    (Faculty of Medicine, University Medical Center Freiburg)

  • B. Bengsch

    (Faculty of Medicine, University Medical Center Freiburg
    University of Freiburg
    German Cancer Consortium (DKTK))

Abstract

The immune-pathology in Crohn’s disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn’s disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6high, CD39, CD69, PD-1, CD27low) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn’s disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions.

Suggested Citation

  • A.-M. Globig & A. V. Hipp & P. Otto-Mora & M. Heeg & L. S. Mayer & S. Ehl & H. Schwacha & M. Bewtra & V. Tomov & R. Thimme & P. Hasselblatt & B. Bengsch, 2022. "High-dimensional profiling reveals Tc17 cell enrichment in active Crohn’s disease and identifies a potentially targetable signature," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31229-z
    DOI: 10.1038/s41467-022-31229-z
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    References listed on IDEAS

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    1. Christina Lückel & Felix Picard & Hartmann Raifer & Lucia Campos Carrascosa & Anna Guralnik & Yajuan Zhang & Matthias Klein & Stefan Bittner & Falk Steffen & Sonja Moos & Federico Marini & Renee Glour, 2019. "IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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