Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production

J Immunol. 2017 Jun 1;198(11):4352-4359. doi: 10.4049/jimmunol.1601792. Epub 2017 May 3.


IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine-secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.

MeSH terms

  • Animals
  • Brefeldin A / pharmacology
  • Cell Differentiation
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Interleukin-2 / metabolism*
  • Interleukin-9 / antagonists & inhibitors
  • Interleukin-9 / biosynthesis*
  • Interleukin-9 / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Monensin / pharmacology
  • Paracrine Communication*
  • Protein Synthesis Inhibitors / pharmacology
  • Proton Ionophores / pharmacology
  • STAT5 Transcription Factor / metabolism
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology*


  • Cytokines
  • Interleukin-2
  • Interleukin-9
  • Protein Synthesis Inhibitors
  • Proton Ionophores
  • STAT5 Transcription Factor
  • Brefeldin A
  • Monensin