Interleukin15

Interleukin-15 (IL-15) is a cytokine of the four-helix bundle family that signals through receptor subunits shared with IL-2. It regulates development, survival, and activation of natural killer (NK) cells and CD8+ memory T cells, supporting cytotoxic functions such as interferon-γ production and granzyme activity, important for defense against intracellular pathogens and tumors.

IL-15 is encoded by the IL15 gene on chromosome 4 and is produced as a precursor processed to a mature protein. It is expressed by monocytes, macrophages, dendritic cells, and some non-hematopoietic cells. A key feature is transpresentation: IL-15 bound to IL-15Rα is presented to neighboring cells expressing the IL-2/15Rβγ receptors.

Signaling through the IL-2/15Rβγ receptor activates JAK-STAT pathways, notably STAT5, promoting NK cell proliferation, CD8+ T cell homeostasis, and cytotoxic maturation. IL-15 can also act as a soluble complex with IL-15Rα. Unlike IL-2, IL-15 does not strongly expand regulatory T cells, giving it a distinct regulatory profile.

Physiologically, IL-15 supports mucosal immunity, tissue-resident NK cells, and memory T cell maintenance. Expression rises during infection or inflammation and can synergize with cytokines like IL-12 and type I interferons. Dysregulated IL-15 signaling has been linked to autoimmune and inflammatory conditions.

Clinically, IL-15–based therapies aim to boost anti-tumor immunity. Agents include IL-15 formulations and IL-15 superagonists designed to mimic transpresentation. Trials assess safety and efficacy in various cancers, with attention to cytokine-related adverse effects and potential neutralizing antibodies.