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

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

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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