IL-15 Signaling

Interleukin 15 (IL-15) belongs to the 4-α-helix bundle family of glycoprotein cytokines that include IL-2, IL-3, IL-4 and IL-21. It exerts profounds effects on the proliferation, survival and differentiation of NK cells and T cells. IL-15 signaling is mainly mediated via a transmembrane heterotrimeric receptor complex that consists of a high affinity ligand binding subunit IL-15Rα and -β and -γ signal transducing subunits. The latter two it shares with IL-2. IL-15 can also signal via an intermediate affinity receptor. Mast cells use a unique receptor, IL-15RX, to mediate signal transduction. IL-15 activates various signaling pathways in different cell types including the JAK/STAT, MAPK and NF-κB pathways to control cell growth and differentiation, enhance phagocytosis and increase the inflammatory response.IL-15 uses juxtacrine and reverse signaling mechanisms in certain cell types, since its major form is membrane-bound, not soluble. For example, reverse signaling occurs in monocytes when the membrane-bound IL-15 is stimulated with soluble IL-15Rα or anti-IL-15 Abs, which can result in activation of ERK, p38MAPK or FAK pathways. In juxtacrine signaling, monocyte membrane-bound IL-15 binds to the receptor complex on neighboring T-cells and initiates signal transduction. (Upgraded 01/2020)