Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2

Immunity. 2011 Mar 25;34(3):409-21. doi: 10.1016/j.immuni.2011.02.011.


T helper 17 (Th17) cell development is driven by cytokines including transforming growth factor-β (TGF-β), interleukin-6 (IL-6), IL-1, and IL-23. Regulatory T (Treg) cells can provide the TGF-β in vitro, but their role in vivo remains unclear, particularly because Treg cells inhibit inflammation in many models of Th17 cell-associated autoimmunity. We used mice expressing Diphtheria toxin receptor under control of the Foxp3 promoter to deplete Foxp3(+) Treg cells in adult mice during in vivo Th17 cell priming. Treg cell depletion resulted in a reduced frequency of antigen-specific IL-17 producers in draining lymph nodes and blood, correlating with reduced inflammatory skin responses. In contrast, Treg cells did not promote IL-17 secretion after initial activation stages. Treg cell production of TGF-β was not required for Th17 cell promotion, and neither was suppression of Th1 cell-associated cytokines. Rather, regulation of IL-2 availability and resultant signaling through CD25 by Treg cells was found to play an important role.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Forkhead Transcription Factors / immunology*
  • Interleukin-17 / immunology*
  • Interleukin-2 / immunology*
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Interleukin-2