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Ogasawara H, Noguchi M. Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells. Cells. 2021;10(11)doi: 10.3390/cells10112906.
Ogasawara, H., & Noguchi, M. (2021). Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells. Cells, 10(11), . https://doi.org/10.3390/cells10112906
Ogasawara, Hiroyuki, and Noguchi, Masato. "Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells." Cells vol. 10,11 (2021). doi: https://doi.org/10.3390/cells10112906
Ogasawara H, Noguchi M. Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells. Cells. 2021 Oct 27;10(11). doi: 10.3390/cells10112906. PMID: 34831128; PMCID: PMC8616451.
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Cells. 2021 Oct 27;10(11). doi: 10.3390/cells10112906.

Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells.

Cells

Hiroyuki Ogasawara, Masato Noguchi

Affiliations

  1. Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan.
  2. Office of Research Development and Sponsored Projects, Shinanomachi Campus, Keio University, Tokyo 160-8582, Japan.

PMID: 34831128 PMCID: PMC8616451 DOI: 10.3390/cells10112906

Abstract

Mast cells (MCs) act as primary effectors in inflammatory and allergic reactions by releasing intracellularly-stored inflammatory mediators in diseases. The two major pathways for MC activation are known to be immunoglobulin E (IgE)-dependent and -independent. Although IgE-dependent signaling is the main pathway to MC activation, IgE-independent pathways have also been found to serve pivotal roles in the pathophysiology of various inflammatory conditions. Recent studies have shown that human and mouse MCs express several regulatory receptors such as toll-like receptors (TLRs), CD48, C300a, and GPCRs, including mas-related GPCR-X2 (MRGPRX2). MRGPRX2 has been reported as a novel GPCR that is expressed in MCs activated by basic secretagogues, neurokinin peptides, host defense antimicrobial peptides, and small molecule compounds (e.g., neuromuscular blocking agents) and leads to MC degranulation and eicosanoids release under in vitro experimental condition. Functional analyses of MRGPRX2 and Mrgprb2 (mouse ortholog) indicate that MRGPRX2 is involved in MC hypersensitivity reactions causing neuroinflammation such as postoperative pain, type 2 inflammation, non-histaminergic itch, and drug-induced anaphylactic-like reactions. In this review, we discuss the roles in innate immunity through functional studies on MRGPRX2-mediated IgE-independent MC activation and also the therapeutic potential of MRGPRX2 inhibitors on allergic and inflammatory diseases.

Keywords: MRGPRX2; MRGPRX2 inhibitor; host defense; mast cell activation; neurogenic inflammation; non-histaminergic itch; pseudoallergic reaction; type 2 inflammation

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