Henriques, C.M., Rino, J., Nibbs, R.J. et al. (2 more authors) (2010) IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Rα in T cells. Blood, 115 (16). pp. 3269-3277. ISSN 0006-4971
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-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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2010 by The American Society of Hematology. This is an author produced version of a paper subsequently published in Blood. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 02 Oct 2015 13:13 |
Last Modified: | 03 Nov 2017 00:47 |
Published Version: | https://doi.org/10.1182/blood-2009-10-246876 |
Status: | Published |
Publisher: | American Society of Hematology |
Refereed: | Yes |
Identification Number: | 10.1182/blood-2009-10-246876 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:88711 |
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