May 2020 — Vol 140 No 5

Drawing of The IgE-mediated versus Mrgprb2-mediated itch axis. Classical activation of mast cells by IgE results in the release of the monoamines such as histamine and serotonin. Mrgprb2 (murine)/MRGPRX2 (human) can be activated by various cationic substances, such as PAMP 9-20, compound 48/80, drugs, NPs, and HDPs. Mrgprb2-mediated activation of mast cells elicits distinct mechanisms of itch from classical IgE stimulation, in which tryptase is a major mediator whereas others such as histamine and serotonin are also included.

The involvement of mediators other than histamine in human itch disorders has long been appreciated. Recent developments in neuroimmune biology have resulted in new insights into itch pathogenesis and treatment. See the concise review by Wang and coworkers on pages 945-951 of this issue for details.