Interleukin-15 signaling pathway (IL-15 pathway)

The Interleukin-15 (IL-15) signaling pathway is a central coordinator of the immune system, essential for the development, survival, and functional activation of natural killer (NK) cells and memory CD8+ T cells (NIH, 2024). Signaling is mediated by a heterotrimeric receptor complex consisting of the high-affinity IL-15Rα subunit, the shared IL-2/IL-15Rβ (CD122) subunit, and the common gamma chain (γc, CD132) (Wikipedia, 2024). A hallmark of this pathway is 'trans-presentation,' a mechanism where IL-15 is presented by IL-15Rα on the surface of one cell to the βγc complex on a neighboring effector cell, activating the JAK/STAT, PI3K/Akt, and MAPK signaling cascades (R&D Systems, 2024). Dysregulation of IL-15 signaling is associated with various pathologies, including autoimmune diseases like celiac disease and alopecia areata, as well as hematological malignancies such as T-cell leukemia and lymphoma (Frontiers in Immunology, 2023). In oncology, the pathway is a high-priority target for immunotherapy, with IL-15 superagonists being developed to enhance anti-tumor immune responses (NIH, 2024). Conversely, antagonists targeting the cytokine or its receptor subunits are being explored to treat chronic inflammatory and autoimmune conditions by dampening excessive lymphocyte activity (NIH, 2024).

Other names

IL-15IL-15RInterleukin-15 receptor complexIL-15/IL-15Rα complex

Agonism of the IL-15 receptor complex to stimulate NK and CD8+ T cell proliferation for cancer therapy; Antagonism of IL-15 or its receptor subunits to inhibit aberrant lymphocyte activation in autoimmune and inflammatory diseases (NIH, 2024; Frontiers in Immunology, 2023).