HIGHLIGHT

Volume 315, Number 17, October 15, 2009

Intracellular IL-15 controls mast cell survival. By Farhad Mirghomizadeh,Supandi Winoto-Morbach, Zane Orinska, Kyeong-Hee Lee, Stefan Schutze, andSilvia Bulfone-Paus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

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Mast cells play an essential role in inflammatory processes. Their phenotype, number, activities,

regulation, and life span are quite heterogeneous between different tissues. Here, we have explored

intracellular stimuli and pathways important in regulating mast cell survival and homeostasis. We

report that intracellular interleukin-15 (IL-15) inhibits mast cell apoptosis and that aged IL-15-

deficient mice show a significantly reduced number of peritoneal mast cells. IL-15-deficient mast

cells show a stronger constitutive expression and enzymatic activity of members of mitochondrial

apoptotic pathways, including cathepsin D, endogenous acid sphingomyelinase, caspase-3 and -7,

and therefore display an increased susceptibility to undergo apoptosis. Therefore, intracellular IL-15

is a novel key regulator of primary mouse mast cell homeostasis in vivo and in vitro.