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

  • Nat Commun. 2022 Jun 27;13(1):3688. doi: 10.1038/s41467-022-31229-z.
A-M Globig  #  1 ,  A V Hipp  #  1 ,  P Otto-Mora  1 ,  M Heeg  2 ,  L S Mayer  1 ,  S Ehl  2  3  4 ,  H Schwacha  1 ,  M Bewtra  5 ,  V Tomov  5 ,  R Thimme  1 ,  P Hasselblatt  1 ,  B Bengsch  6  7  8
Affiliations
  • 1. Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
  • 2. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
  • 3. Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
  • 4. German Cancer Consortium (DKTK), Heidelberg, Germany.
  • 5. Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 6. Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany. [email protected].
  • 7. Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany. [email protected].
  • 8. German Cancer Consortium (DKTK), Heidelberg, Germany. [email protected].
  • # Contributed equally.
PMID: 35760777 DOI: 10.1038/s41467-022-31229-z
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.

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