Activation of Mast-Cell-Expressed Mas-Related G-Protein-Coupled Receptors Drives Non-histaminergic Itch

James Meixiong, Michael Anderson, Nathachit Limjunyawong, Mark F. Sabbagh, Eric Hu, Madison R. Mack, Landon K. Oetjen, Fang Wang, Brian S. Kim, Xinzhong Dong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1163-1171.e5
JournalImmunity
Volume50
Issue number5
DOIs
StatePublished - May 21 2019

Keywords

  • GPCR
  • MRGPRX2
  • Mrgpr
  • Mrgprb2
  • histamine
  • itch
  • mast cell
  • pruritus
  • receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Meixiong, J., Anderson, M., Limjunyawong, N., Sabbagh, M. F., Hu, E., Mack, M. R., Oetjen, L. K., Wang, F., Kim, B. S., & Dong, X. (2019). Activation of Mast-Cell-Expressed Mas-Related G-Protein-Coupled Receptors Drives Non-histaminergic Itch. Immunity, 50(5), 1163-1171.e5. https://doi.org/10.1016/j.immuni.2019.03.013