Mast cell associated pruritus

Mast cells are granule-enriched innate immune cells located at the interface between the organism and the environment. As sentinel immune cells, mast cells are served by their ability to sense disparate noxious compounds through receptors ranging from the well-studied high-affinity IgE receptor, Fc epsilon RI (FcεRI), to G protein-coupled receptors (GPCR) such as MRGPR X2. Receptor activation of mast cells results in degranulation and release of numerous bioactive molecules. In the skin, mast cells are closely associated with sensory nerves. Given this relationship, mast cells and nerves have been functionally linked in acute and chronic pruritus. In this chapter, we will review the contribution of mast cells to acute and chronic itch by discussing the breadth of their receptors, intracellular signaling mechanisms, and degranulation, allowing cross-talk between mast cells and nerves. Through this lens, we hope to convey the importance of this relationship in clinically relevant pruritus.