TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells

Immunity. 2006 Feb;24(2):179-89. doi: 10.1016/j.immuni.2006.01.001.

Abstract

We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4+ CD25+ T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism*
  • Dendritic Cells / immunology
  • Interleukin-17 / biosynthesis*
  • Lymphocyte Subsets / immunology*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Interleukin-1 / physiology
  • Smad7 Protein / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Transforming Growth Factor beta / physiology*
  • Transforming Growth Factor beta1

Substances

  • Cytokines
  • Interleukin-17
  • Membrane Glycoproteins
  • Receptors, Interleukin-1
  • Smad7 Protein
  • TIRAP protein, mouse
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1