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

Hai-Hui Xue; Panu E Kovanen; Cynthia A Pise-Masison; Maria Berg; Michael F Radovich; John N Brady; Warren J Leonard

doi:10.1073/pnas.212214999

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.

Authors

Hai-Hui Xue¹, Panu E Kovanen, Cynthia A Pise-Masison, Maria Berg, Michael F Radovich, John N Brady, Warren J Leonard

Affiliation

¹ Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, MD 20892-1674, USA.

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