High-dimensional profiling reveals Tc17 cell enrichment in active Crohn's disease and identifies a potentially targetable signature.
Where this comes from
- Record sourced from PubMed, PMID 35760777.
- Also identified by DOI 10.1038/s41467-022-31229-z and PMC identifier 9237103.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (CD6<sup>high</sup>, CD39, CD69, PD-1, CD27<sup>low</sup>) 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.
Medical subject headings
- Crohn Disease
- Interleukin-17