IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Ralpha in T cells

Blood. 2010 Apr 22;115(16):3269-77. doi: 10.1182/blood-2009-10-246876. Epub 2010 Feb 26.


Interleukin-7 (IL-7) is an essential cytokine for T-cell development and homeostasis. It is well established that IL-7 promotes the transcriptional down-regulation of IL7RA, leading to decreased IL-7Ralpha surface expression. However, it is currently unknown whether IL-7 regulates the intracellular trafficking and early turnover of its receptor on ligand binding. Here, we show that, in steady-state T cells, IL-7Ralpha is slowly internalized and degraded while a significant fraction recycles back to the surface. On IL-7 stimulation, there is rapid IL-7Ralpha endocytosis via clathrin-coated pits, decreased receptor recycling, and accelerated lysosome and proteasome-dependent degradation. In accordance, the half-life of IL-7Ralpha decreases from 24 hours to approximately 3 hours after IL-7 treatment. Interestingly, we further demonstrate that clathrin-dependent endocytosis is necessary for efficient IL-7 signal transduction. In turn, pretreatment of T cells with JAK3 or pan-JAK inhibitors suggests that IL-7Ralpha degradation depends on the activation of the IL-7 signaling effector JAK3. Overall, our findings indicate that IL-7 triggers rapid IL-7Ralpha endocytosis, which is required for IL-7-mediated signaling and subsequent receptor degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Separation
  • Clathrin-Coated Vesicles / immunology
  • Clathrin-Coated Vesicles / metabolism*
  • Endocytosis / physiology
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Interleukin-7 / immunology
  • Interleukin-7 / metabolism*
  • Janus Kinase 3 / immunology
  • Janus Kinase 3 / metabolism*
  • Microscopy, Confocal
  • Protein Transport / physiology
  • Receptors, Interleukin-7 / immunology
  • Receptors, Interleukin-7 / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Interleukin-7
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain
  • JAK3 protein, human
  • Janus Kinase 3