IFN-γ and IL-12 synergize to convert in vivo generated Th17 into Th1/Th17 cells

Eur J Immunol. 2010 Nov;40(11):3017-27. doi: 10.1002/eji.201040539.


Th1 and Th17 cells are distinct lineages of effector/memory cells, imprinted for re-expression of IFN-γ and IL-17, by upregulated expression of T-bet and retinoic acid-related orphan receptor γt (RORγt), respectively. Apparently, Th1 and Th17 cells share tasks in the control of inflammatory immune responses. Th cells coexpressing IFN-γ and IL-17 have been observed in vivo, but it remained elusive, how these cells had been generated and whether they represent a distinct lineage of Th differentiation. It has been shown that ex vivo isolated Th1 and Th17 cells are not interconvertable by TGF-β/IL-6 and IL-12, respectively. Here, we show that ex vivo isolated Th17 cells can be converted into Th1/Th17 cells by combined IFN-γ and IL-12 signaling. IFN-γ is required to upregulate expression of the IL-12Rβ2 chain, and IL-12 for Th1 polarization. These Th1/Th17 cells stably coexpress RORγt and T-bet at the single-cell level. Our results suggest a molecular pathway for the generation of Th1/Th17 cells in vivo, which combine the pro-inflammatory potential of Th1 and Th17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Gene Expression Regulation / immunology
  • Humans
  • Interferon-gamma / agonists
  • Interferon-gamma / immunology*
  • Interleukin-12 / agonists
  • Interleukin-12 / immunology*
  • Interleukin-6 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Receptors, Interleukin-12 / immunology
  • Signal Transduction / immunology*
  • T-Box Domain Proteins / immunology
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Transforming Growth Factor beta / immunology


  • IL12RB2 protein, human
  • IL6 protein, human
  • Il12rb2 protein, mouse
  • Interleukin-6
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Interleukin-12
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transforming Growth Factor beta
  • Interleukin-12
  • Interferon-gamma