Interleukin-2 and Interleukin-2 receptor axis (IL-2/IL-2R axis)

The Interleukin-2 (IL-2) and Interleukin-2 receptor (IL-2R) axis is a fundamental signaling pathway in the immune system that governs the expansion and function of various lymphocyte subsets [1, 7]. The axis comprises the IL-2 cytokine and its multi-subunit receptor, which exists in low, intermediate, and high-affinity forms depending on the combination of alpha (CD25), beta (CD122), and common gamma (CD132) chains [4, 11]. High-affinity signaling is critical for the development and homeostasis of regulatory T cells (Tregs), which maintain peripheral tolerance, whereas intermediate-affinity signaling primarily drives the proliferation of effector T cells and natural killer (NK) cells [12, 16]. Dysregulation of this axis is a hallmark of many diseases, including metastatic melanoma, renal cell carcinoma, and autoimmune conditions like multiple sclerosis [1, 9]. Therapeutic interventions target this axis through either agonism to enhance anti-tumor immunity or antagonism to prevent organ transplant rejection and treat autoimmune flares [5, 10]. Despite its therapeutic potential, the axis presents significant challenges, most notably the risk of severe systemic toxicities like vascular leak syndrome and the difficulty of achieving cell-type-specific modulation [5, 14].

Other names

IL-2 signaling pathwayCD25/CD122/CD132 complexIL-2/IL-2R systemInterleukin-2 receptor complex

Agonism of the IL-2 receptor to stimulate T-cell and NK-cell proliferation for oncology, or antagonism of the IL-2 receptor alpha subunit to inhibit T-cell activation for immunosuppression and treatment of autoimmune diseases.