CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model

Immunity. 2011 Mar 25;34(3):422-34. doi: 10.1016/j.immuni.2011.03.002.

Abstract

Th17 cells and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are thought to promote and suppress inflammatory responses, respectively. Here we explore why under Th17 cell polarizing conditions, Treg cells did not suppress, but rather upregulated, the expression of interleukin-17A (IL-17A), IL-17F, and IL-22 from responding CD4(+) T cells (Tresp cells). Upregulation of IL-17 cytokines in Tresp cells was dependent on consumption of IL-2 by Treg cells, especially at early time points both in vitro and in vivo. During an oral Candida albicans infection in mice, Treg cells induced IL-17 cytokines in Tresp cells, which markedly enhanced fungal clearance and recovery from infection. These findings show how Treg cells can promote acute Th17 cell responses to suppress mucosal fungus infections and reveal that Treg cells have a powerful capability to fight infections besides their role in maintaining tolerance or immune homeostasis.

Publication types

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

MeSH terms

  • Animals
  • CD4 Antigens / immunology*
  • Candida albicans / immunology
  • Candidiasis / immunology*
  • Cell Differentiation
  • Disease Models, Animal
  • Forkhead Transcription Factors / immunology*
  • Immunity, Innate*
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit