TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells

Eur J Immunol. 2009 Jan;39(1):207-15. doi: 10.1002/eji.200838748.


Human Th17 clones and circulating Th17 cells showed lower susceptibility to the anti-proliferative effect of TGF-beta than Th1 and Th2 clones or circulating Th1-oriented T cells, respectively. Accordingly, human Th17 cells exhibited lower expression of clusterin, and higher Bcl-2 expression and reduced apoptosis in the presence of TGF-beta, in comparison with Th1 cells. Umbilical cord blood naïve CD161(+)CD4(+) T cells, which contain the precursors of human Th17 cells, differentiated into IL-17A-producing cells only in response to IL-1beta plus IL-23, even in serum-free cultures. TGF-beta had no effect on constitutive RORgamma t expression by umbilical cord blood CD161(+) T cells but it increased the relative proportions of CD161(+) T cells differentiating into Th17 cells in response to IL-1beta plus IL-23, whereas under the same conditions it inhibited both T-bet expression and Th1 development. These data suggest that TGF-beta is not critical for the differentiation of human Th17 cells, but indirectly favors their expansion because Th17 cells are poorly susceptible to its suppressive effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Clusterin / immunology
  • Clusterin / metabolism
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology*
  • Interleukin-1beta / pharmacology
  • Interleukin-23 / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / pharmacology


  • CLU protein, human
  • Clusterin
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta