IL15R

The interleukin-15 receptor (IL-15R) is a cytokine receptor system that binds interleukin-15 (IL-15) and mediates signaling important for innate and adaptive immune responses. In humans, the functional IL-15 receptor complex comprises the IL-15 receptor alpha chain (IL-15Rα, CD215) and the signaling subunits IL-2/15 receptor beta chain (IL-2/15Rβ, CD122) together with the common gamma chain (γc, CD132). IL-15Rα can exist as a membrane-bound form or be shed as a soluble receptor that binds IL-15 and influences its bioavailability. The IL-2/15Rβ and γc subunits are shared with other cytokine receptors, and they transmit signals upon engagement with IL-15–bound IL-15Rα or in complex with the IL-15–IL-15Rα assembly on presenting cells.

Mechanism and signaling occur primarily through JAK-STAT pathways, leading to the activation, proliferation, and survival of natural killer (NK) cells and memory CD8+ T cells. A notable feature is trans-presentation, where IL-15 bound to IL-15Rα on one cell presents the cytokine to neighboring cells expressing IL-2/15Rβ and γc, enabling targeted immune activation without broad systemic exposure.

Expression of IL-15R components is widespread, with notable activity in dendritic cells, macrophages, and other antigen-presenting cells, and it is regulated by inflammatory cues. Functionally, IL-15R signaling supports NK cell development, maintenance of memory CD8+ T cells, and homeostasis of mucosal and tissue-resident lymphocytes.

Clinical relevance includes exploration of IL-15 and IL-15R–targeted therapies in cancer immunotherapy and autoimmune diseases. IL-15–based agonists and IL-15R modulators aim to enhance anti-tumor immunity or to mitigate pathological immune activation in certain contexts.