Waickman, AT, Keller, HR, Kim, T-H et al. (6 more authors) (2020) The cytokine receptor IL-7Rα impairs IL-2 receptor signaling and constrains the in vitro differentiation of Foxp3+ Treg cells. iScience, 23 (8). 101421. ISSN 2589-0042
Abstract
IL-7 receptor signaling is essential for the generation and maintenance of conventional T cells. Immunosuppressive Foxp3+ Treg cells, however, express uniquely low amounts of the IL-7-proprietary IL-7Rα so that they are impaired in IL-7 signaling. Because Treg cells depend on IL-2, the loss of IL-7Rα has been considered irrelevant for Treg cells. In contrast, here, we report that IL-7Rα downregulation is necessary to maximize IL-2R signaling. While IL-7Rα overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells. Mechanistically, we found that γc, which is a receptor subunit shared by IL-7R and IL-2R, directly binds and pre-associates with IL-7Rα, thus limiting its availability for IL-2R binding. Consequently, overexpression of signaling-deficient, tailless IL-7Rα proteins inhibited IL-2R signaling, demonstrating that IL-7Rα sequesters γc and suppresses IL-2R signaling by extracellular interactions. Collectively, these results reveal a previously unappreciated regulatory mechanism of IL-2 receptor signaling that is governed by IL-7Rα abundance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020, Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | common γ-chain; STAT5; T cells; Th17 cells |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mathematics (Leeds) > Applied Mathematics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 29 Jul 2020 11:03 |
Last Modified: | 25 Jun 2023 22:22 |
Status: | Published |
Publisher: | Cell Press |
Identification Number: | 10.1016/j.isci.2020.101421 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:163803 |