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

Henriques, C. M., Rino, J., Nibbs, R. J. , Graham, G. J. and Barata, J. T. (2010) IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7R alpha in T cells. Blood, 115(16), pp. 3269-3277. (doi: 10.1182/blood-2009-10-246876)

Abstract

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-7R alpha 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-7R alpha is slowly internalized and degraded while a significant fraction recycles back to the surface. On IL-7 stimulation, there is rapid IL-7R alpha endocytosis via clathrin-coated pits, decreased receptor recycling, and accelerated lysosome and proteasome-dependent degradation. In accordance, the half-life of IL-7R alpha 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-7R alpha degradation depends on the activation of the IL-7 signaling effector JAK3. Overall, our findings indicate that IL-7 triggers rapid IL-7R alpha endocytosis, which is required for IL-7-mediated signaling and subsequent receptor degradation. (Blood. 2010; 115(16): 3269-3277)

• Item Type: Articles
• Keywords: ACUTE LYMPHOBLASTIC-LEUKEMIA ALPHA BETA-CHAIN BINDING BLOOD CELLS CYCLE PROGRESSION DEFICIENT MICE DOWN-REGULATION ENDOCYTIC PATHWAYS EXPRESSION GENE-EXPRESSION growth HUMAN PLASMA immunity INHIBITOR INHIBITORS INTERLEUKIN-2 RECEPTOR LIGAND Proteasome RECEPTOR RECEPTOR-GAMMA CHAIN STIMULATION SURFACE T cells T-cell T-CELLS Treatment TRENDS UNIT
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nibbs, Professor Rob and Graham, Professor Gerard
• Authors: Henriques, C. M., Rino, J., Nibbs, R. J., Graham, G. J., and Barata, J. T.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Blood
• Publisher: American Society of Hematology
• ISSN: 0006-4971
• ISSN (Online): 1528-0020