Interleukin-2 signaling pathway (IL-2/IL-2R pathway)

The Interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression pathways are fundamental to the regulation of the adaptive immune system, specifically governing the expansion and function of T lymphocytes (StatPearls, 2023). Upon T-cell receptor (TCR) stimulation, the activation of calcineurin leads to the dephosphorylation of NFAT, which translocates to the nucleus to induce the transcription of the IL-2 gene (UniProt P60568). Concurrently, activation signals trigger the expression of the high-affinity IL-2 receptor alpha chain (CD25), which combines with the constitutive beta (CD122) and gamma (CD132) chains to form the functional heterotrimeric receptor complex (PubMed, PMID: 22343569). Binding of IL-2 to this receptor activates the JAK-STAT5, PI3K/Akt, and MAPK signaling pathways, promoting T-cell survival and proliferation (NIH, 2022). This pathway is a critical therapeutic target in transplantation and autoimmunity, where drugs like Cyclosporine and Tacrolimus inhibit IL-2 production, and monoclonal antibodies like Basiliximab block the IL-2 receptor (PubChem, CID 5284373). In oncology, recombinant IL-2 (Aldesleukin) is utilized to enhance anti-tumor immunity, although its use is limited by severe side effects such as capillary leak syndrome (Wikipedia, Interleukin 2).

Other names

IL-2/IL-2R axisT-cell growth factor signaling pathwayInterleukin-2 production and signaling cascadeIL-2/CD25 signaling

Inhibition of calcineurin to prevent NFAT-mediated IL-2 transcription; competitive antagonism of the IL-2 receptor alpha chain (CD25) to block T-cell proliferation; agonism of the IL-2 receptor to stimulate anti-tumor immune responses; and inhibition of the downstream mTOR pathway to arrest the cell cycle.