The pleiotropic cytokine interleukin-2 (IL-2) is an integral regulator of healthy and pathological immune responses, with the most important role in regulating the homeostasis of regulatory T cells. IL-2 signalling involves three distinct receptors: The IL-2 receptor α (IL-2Rα/CD25), IL-2Rβ, and IL-2Rγ/γc . While IL-2Rβ and γc are essential for signal transduction, IL-2Rα regulates the affinity of the receptor complex towards IL-2. A soluble form of the IL-2Rα (sIL-2Rα) is present in the blood of healthy individuals and increased under various pathological conditions. Although it is known that the sIL-2Rα retains its ability to bind IL-2, it is not fully understood how this molecule affects IL-2 function and thus immune responses. Here, we summarize the current knowledge on the generation and function of the sIL-2Rα. We describe the molecular mechanisms leading to sIL-2Rα generation and discuss the different IL-2 modulating functions that have been attributed to the sIL-2Rα. Finally, we describe attempts to utilize the sIL-2Rα as a therapeutic tool.
Keywords: CD25; interleukin-2; interleukin-2 receptor; proteolysis; regulatory T cells.
© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.