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

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. Although 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 sign

SUBMITTER: Waickman AT 

PROVIDER: S-EPMC7424196 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature