Interleukin-2 receptor alpha (IL-2Rα), also known as CD25, is a type I transmembrane glycoprotein that constitutes the α-chain of the trimeric interleukin-2 (IL-2) receptor complex. Structurally, CD25 comprises a large extracellular domain responsible for IL-2 binding, a single transmembrane region, and a short cytoplasmic tail that lacks intrinsic signaling motifs. Consequently, CD25 does not directly mediate intracellular signal transduction but primarily functions to increase the affinity of the IL-2 receptor for its ligand (1). During thymic T-cell development, CD25 expression marks intermediate CD4−CD8− double-negative thymocyte populations, particularly the DN2 and DN3 stages (2). CD25 is also constitutively expressed at variable levels on regulatory T cells (Tregs) (3,4). High CD25 expression on Foxp3⁺ Tregs is associated with potent immunosuppressive activity and has been linked to poor prognosis in colorectal cancer (5). In contrast, Foxp3⁺ Tregs residing in the small intestinal epithelium markedly downregulate CD25 expression and persist independently of IL-2 while retaining strong suppressive function (4).
Beyond its membrane-bound form, CD25 also exists as a soluble receptor generated through proteolytic shedding. Circulating levels of soluble CD25 are dysregulated in numerous pathological conditions, including cancer, inflammatory diseases, and autoimmune disorders, highlighting its relevance as a biomarker of immune activation (1).
