Beyond classical immunity: Mast cells as signal converters between tissues and neurons

Mast cells are regarded as effectors in immune defense against parasites and venoms and play an essential role in the pathology of allergic diseases. More recently, mast cells have been shown to receive stimuli derived from type 2 immunity, tissue damage, stress, and inflammation. Mast cells then rapidly convert these diverse signals into appropriate, organ-specific protective reflexes that can limit inflammation or reduce tissue damage. In this review, we consider functions of mast cells in sensations-such as pain, itch, and nausea-arising from tissue insults and inflammation and the ensuing protective responses. In light of emerging data highlighting the involvement of mast cells in neuroimmune communication, we also propose that mast cells are "signal converters" linking immunological and tissue states with nervous system responses.