Mast cell signaling and its role in urticaria.

Chronic urticaria (CU) is a mast cells (MC)-driven disease characterized by the development of itching wheals and/or angioedema. In the last decades, outstanding progress has been made in defining the mechanisms involved in MC activation, and novel activating and inhibitory receptors expressed in MC surface were identified and characterized. Besides an IgE-mediated activation via FcεRI-cross-linking, other activating receptors, including Mas-related G protein-coupled receptor-X2 (MRGPRX2), C5a receptor and protease-activated receptors (PAR1 and PAR2) are responsible for MC activation. This would partly explain why some subgroups of chronic spontaneous urticaria (CSU), the most frequent form of urticaria in the general population, do not respond to IgE target therapies, requiring other therapeutic approaches for improving the management of the disease. In this review we shed some light on the current knowledge of the immunological and non-immunological mechanisms regulating MC activation in CSU, taking in account the complex inflammatory scenario underlying CSU pathogenesis, and novel potential MC targeted therapies, including surface receptors and cytoplasmic signaling proteins.