Interleukin-2 signaling pathway components (IL-2 signaling pathway)

The Interleukin-2 (IL-2) signaling pathway is a fundamental regulator of the adaptive immune system, primarily governing the expansion and function of T lymphocytes and natural killer (NK) cells (Wikipedia, 2024). Signaling is initiated when the cytokine IL-2 binds to its multi-subunit receptor complex, which can exist as a low-affinity monomer (CD25), an intermediate-affinity dimer (CD122 and CD132), or a high-affinity trimer (CD25, CD122, and CD132) (UniProt, 2024). This binding triggers the activation of associated Janus kinases, JAK1 and JAK3, which in turn phosphorylate the signal transducer and activator of transcription 5 (STAT5), as well as the PI3K/Akt and MAPK/ERK pathways (NIH, 2024). The pathway serves a dual role: high-affinity signaling on regulatory T cells (Tregs) maintains immune tolerance, while signaling on effector T cells and NK cells promotes robust anti-pathogen and anti-tumor responses (R&D Systems, 2024). Dysregulation of IL-2 signaling is implicated in various pathologies, including autoimmune diseases like multiple sclerosis and type 1 diabetes, as well as hematologic and solid malignancies (PubMed, 2024). Consequently, the pathway is a major therapeutic target, with drugs ranging from IL-2 agonists for cancer immunotherapy to IL-2 receptor antagonists and JAK inhibitors for treating transplant rejection and inflammatory conditions (StatPearls, 2024).

Other names

IL-2/IL-2R systemIL-2 receptor complexIL-2/JAK/STAT pathwayInterleukin-2 receptor signaling

The pathway is modulated through various mechanisms: IL-2 receptor agonism (e.g., aldesleukin) to stimulate immune responses in cancer; IL-2 receptor antagonism (e.g., basiliximab) to suppress T-cell activation in transplantation; and inhibition of downstream kinases like JAK1 and JAK3 (e.g., tofacitinib) to treat inflammatory and autoimmune disorders.