Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation

Immunity. 2007 Mar;26(3):371-81. doi: 10.1016/j.immuni.2007.02.009.

Abstract

Recent work has identified a new subset of effector T cells that produces interleukin (IL)-17 known as T helper 17 (Th17) cells, which is involved in the pathophysiology of inflammatory diseases and is thought to be developmentally related to regulatory T (Treg) cells. Because of its importance for Treg cells, we examined the role of IL-2 in Th17 generation and demonstrate that a previously unrecognized aspect of IL-2 function is to constrain IL-17 production. Genetic deletion or antibody blockade of IL-2 promoted differentiation of the Th17 cell subset. Whereas STAT3 appeared to be a key positive regulator of RORgammat and IL-17 expression, absence of IL-2 or disruption of its signaling by deletion of the transcription factor STAT5 resulted in enhanced Th17 cell development. We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-2 / genetics
  • Interleukin-2 / pharmacology
  • Interleukin-2 / physiology*
  • Lymphocyte Activation / genetics*
  • Mice
  • Mice, Mutant Strains
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / physiology
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / physiology*
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Interleukin-17
  • Interleukin-2
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor