IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes

Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13759-64. doi: 10.1073/pnas.212214999. Epub 2002 Sep 27.

Abstract

Interleukin (IL)-2 is a type I four-alpha-helical bundle cytokine that plays vital roles in antigen-mediated proliferation of peripheral blood T cells and also is critical for activation-induced cell death. We now demonstrate that IL-2 potently decreases expression of IL-7 receptor alpha chain (IL-7Ralpha) mRNA and protein. The fact that IL-7Ralpha is a component of the receptors for both IL-7 and thymic stromal lymphopoietin (TSLP) suggests that IL-2 can negatively regulate signals by each of these cytokines. Previously it was known that the IL-2 and IL-7 receptors shared the common cytokine receptor gamma chain, gamma(c), which suggested a possible competition between these cytokines for a receptor component. Our findings now suggest a previously unknown type of cross-talk between IL-2 and IL-7 signaling by showing that IL-2 signaling can diminish IL-7Ralpha expression via a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

MeSH terms

  • Animals
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk Proteins*
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / metabolism*
  • STAT5 Transcription Factor
  • Signal Transduction
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Trans-Activators / deficiency
  • Trans-Activators / genetics

Substances

  • DNA-Binding Proteins
  • Interleukin-2
  • Milk Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Interleukin-7
  • STAT5 Transcription Factor
  • Trans-Activators
  • interleukin-7 receptor, alpha chain
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt