| First Author | Waickman AT | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 8 | Pages | 101421 |
| PubMed ID | 32791329 | Mgi Jnum | J:306927 |
| Mgi Id | MGI:6718113 | Doi | 10.1016/j.isci.2020.101421 |
| Citation | Waickman AT, et al. (2020) The Cytokine Receptor IL-7Ralpha Impairs IL-2 Receptor Signaling and Constrains the In Vitro Differentiation of Foxp3(+) Treg Cells. iScience 23(8):101421 |
| abstractText | 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-7Ralpha so that they are impaired in IL-7 signaling. Because Treg cells depend on IL-2, the loss of IL-7Ralpha has been considered irrelevant for Treg cells. In contrast, here, we report that IL-7Ralpha downregulation is necessary to maximize IL-2R signaling. Although IL-7Ralpha overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells. Mechanistically, we found that gammac, which is a receptor subunit shared by IL-7R and IL-2R, directly binds and pre-associates with IL-7Ralpha, thus limiting its availability for IL-2R binding. Consequently, overexpression of signaling-deficient, tailless IL-7Ralpha proteins inhibited IL-2R signaling, demonstrating that IL-7Ralpha sequesters gammac 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-7Ralpha abundance. |
