Genetic proof for the transient nature of the Th17 phenotype

IL‐17‐producing CD4+ T cells (Th17) have been classified as a new T helper cell subset. Using an IL‐17 fate mapping mouse strain, which genetically fixes the memory of IL‐17 expression, we demonstrate that IL‐17A/F‐expressing T helper cells generated either in vitro or in vivo are not a stable T‐cell subset. Upon adoptive transfer of IL‐17F‐reporter‐positive Th17 cells to RAG‐deficient or WT animals, encephalitogenic Th17 cells partially lose IL‐17 expression and upregulate IFN‐γ. Additionally, we show that Th1 cells can convert in vivo to IL‐17A/IFN‐γ‐coexpressing cells in the mesenteric lymph nodes (mLN). Our data classify IL‐17A and IL‐17F as cytokines produced transiently in response to the local microenvironment, thus showing that IL‐17 expression does not define an end‐stage T helper cell subset.