The Cytokine Receptor IL-7Rα Impairs IL-2 Receptor Signaling and Constrains the In Vitro Differentiation of Foxp3+ Treg Cells

• DOI: 10.1016/j.isci.2020.101421
• Publication Date: 2020-07-29T01:32:50Z
• Authors: Adam T. Waickman; Hilary R. Keller; Tae-Hyoun Kim; Megan A. Luckey; Xuguang Tai; Changwan Hong; Carmen Molina-París; Scott T.R. Walsh; Jung-Hyun Park
• Keywords: Cytokine receptor

IL-7 receptor signaling is essential for the generation and maintenance of conventional T cells. Immunosuppressive Foxp3+ Treg cells, however, express uniquely low amounts IL-7-proprietary IL-7Rα so that they are impaired in signaling. Because cells depend on IL-2, loss has been considered irrelevant In contrast, here, we report downregulation necessary to maximize IL-2R Although overexpression promoted signaling, unexpectedly, IL-2 was suppressed same Mechanistically, found γc, which a subunit shared by IL-7R IL-2R, directly binds pre-associates with IL-7Rα, thus limiting its availability binding. Consequently, signaling-deficient, tailless proteins inhibited demonstrating sequesters γc suppresses extracellular interactions. Collectively, these results reveal previously unappreciated regulatory mechanism governed abundance.