New roles and controls of mast cells.

Mast cells are innate immune cells implicated in immune surveillance and defense. They are filled with secretory granules where a vast array of molecules endowed with multiple biological activities are stored. The process of granule secretion, named degranulation, is a tightly controlled biological phenomenon that allows mast cells to rapidly and efficiently release bioactive mediators in response to extracellular stimuli. MC degranulation allows fighting pathogens, limiting envenomation and contributes to tissue homeostasis. However, it is also a potentially harmful response that plays a key role in the development of allergy and inflammatory diseases. Recent findings revealed that MC degranulation is a complex modular process that can be controlled at multiple levels. First, mast cells can decode different activation stimuli into two main patterns of degranulation that differently impact inflammatory responses. Second, mast cells in contact with antibody-opsonized cells or parasites form antibody-dependent degranulatory synapse for dedicated secretion and defense. Third, IL-33 fine-tunes FcR-mediated degranulation at the single cell level. Together these recent findings show how mast cells adapt their degranulation responses to environmental cues and highlight the remarkable functional plasticity of these cells.