Genetic proof for the transient nature of the Th17 phenotype

Eur J Immunol. 2010 Dec;40(12):3336-46. doi: 10.1002/eji.201040755.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Genes, RAG-1 / genetics
  • Genes, Reporter / genetics
  • Integrases / genetics
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Th17 Cells / pathology


  • Receptors, Antigen, T-Cell
  • Interferon-gamma
  • Cre recombinase
  • Integrases