Are we ready to downregulate mast cells?

Downregulation of mast cells (MCs) function and/or survival is warranted in allergic inflammation (AI), mastocytosis/MC leukemias and in other inflammatory diseases in which MCs have a central role. Human MCs (hMCs) have been recently shown to express the death receptor (DR) TRAIL and the inhibitory receptors (IRs) CD300a and Siglec-8. TRAIL is the only known DR functional on hMCs, and interestingly its function is upregulated by IgE-dependent MC activation. The newly described IRs, CD300a and Siglec-8, potently downregulate MC activation and survival in vitro and inhibit different IgE-mediated responses in vivo. Therefore a selective targeting of TRAIL and of IRs on MC could be a novel immunopharmacological way to downregulate MC-associated diseases.