Th17 Cells Are Long Lived and Retain a Stem Cell-like Molecular Signature

SummaryTh17 cells have been described as short lived, but this view is at odds with their capacity to trigger protracted damage to normal and transformed tissues. We report that Th17 cells, despite displaying low expression of CD27 and other phenotypic markers of terminal differentiation, efficiently eradicated tumors and caused autoimmunity, were long lived, and maintained a core molecular signature resembling early memory CD8+ cells with stem cell-like properties. In addition, we found that Th17 cells had high expression of Tcf7, a direct target of the Wnt and β-catenin signaling axis, and accumulated β-catenin, a feature observed in stem cells. In vivo, Th17 cells gave rise to Th1-like effector cell progeny and also self-renewed and persisted as IL-17A-secreting cells. Multipotency was required for Th17 cell-mediated tumor eradication because effector cells deficient in IFN-γ or IL-17A had impaired activity. Thus, Th17 cells are not always short lived and are a less-differentiated subset capable of superior persistence and functionality.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (308 K)Download as PowerPoint slideHighlights► Despite low CD27 expression, Th17 cells are long lived and efficiently kill tumor ► Th17 cell-derived cells share a core molecular signature with early memory CD8+ T cells ► Unlike Th1 cells, Th17 cells express high Tcf7 and stable β-catenin ► Th17 cells have stem cell-like attributes of self-renewal and multipotency