Classical itch studies have focused on immunoglobulin E (IgE)-mediated mast cell activation and histamine release. Recently， members of the Mas-related G-protein-coupled receptor (Mrgpr) family have been identified as mast cell receptors， but their role in itch is unclear. Here， we report that mast cell activation via Mrgprb2 evoked non-histaminergic itch in mice independently of the IgE-Fc epsilon RI (FcεRI)-histamine axis. Compared with IgE-FcεRI stimulation， Mrgprb2 activation of mast cells was distinct in both released substances (histamine， serotonin， and tryptase) and the pattern of activated itch-sensory?neurons. Mrgprb2 deficiency decreased itch in multiple preclinical models of allergic c... More
Classical itch studies have focused on immunoglobulin E (IgE)-mediated mast cell activation and histamine release. Recently， members of the Mas-related G-protein-coupled receptor (Mrgpr) family have been identified as mast cell receptors， but their role in itch is unclear. Here， we report that mast cell activation via Mrgprb2 evoked non-histaminergic itch in mice independently of the IgE-Fc epsilon RI (FcεRI)-histamine axis. Compared with IgE-FcεRI stimulation， Mrgprb2 activation of mast cells was distinct in both released substances (histamine， serotonin， and tryptase) and the pattern of activated itch-sensory?neurons. Mrgprb2 deficiency decreased itch in multiple preclinical models of allergic contact dermatitis (ACD)， a pruritic inflammatory skin disorder， and both mast cell number and PAMP1-20 concentrations (agonist of the human Mrgprb2 homolog， MRGPRX2) were increased in human ACD skin. These findings suggest that this pathway may represent a therapeutic target for treating ACD and mast-cell-associated itch disorders in which antihistamines are ineffective.
