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

The T cell compartment in patients with Crohn's disease is dysregulated. Here the authors use cytometric profiling to reveal an enrichment of distinct Tc17 cells during active Crohn's disease and may suggest CD6 as a potential target for therapeutic studies. 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 (CD6(high), CD39, CD69, PD-1, CD27(low)) 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-gamma 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.

Automated summary

The T cell compartment in patients with Crohn's disease is dysregulated, and an enrichment of Tc17 cells during active disease suggests CD6 as a potential therapeutic target. The identified Tc17 signature may guide personalized treatment decisions in Crohn's disease.