4.7 Review

Mas-related G protein-coupled receptor X2 and its activators in dermatologic allergies

Journal

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 147, Issue 2, Pages 456-469

Publisher

MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2020.08.027

Keywords

MRGPRX2; MRGX2; agonists; chronic spontaneous urticaria; atopic dermatitis; substance P; neuropeptides; eosinophil granule proteins; antimicrobial peptides; pruritus; itch

Funding

  1. Russian Academic Excellence Project 5-100
  2. German Research Foundation [KR3618/3-1 [2690], KR3618/5-1, BA3769/4-1]
  3. Interdisciplinary Center for Clinical Research at the Friedrich Alexander University of Erlangen-Nurnberg [E20, E27]
  4. GA2LEN network of Urticaria Centers of Reference and Excellence (UCARE)
  5. Bavarian Equal Opportunities Sponsorship (Realisierung von Chancengleichheit von Frauen in Forschung und Lehre-Realization Equal Opportunities for Women in Research and Teaching)
  6. GA2LEN fellowship

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MRGPRX2 is a multiligand receptor highly expressed on skin mast cells, whose agonists may serve as potential biomarkers for the progression of cutaneous inflammatory diseases and response to treatment in patients with inflammatory and pruritic skin diseases.
The Mas-related G protein-coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin mast cells and the levels of the MRGPRX2 agonists (eg, substance P, major basic protein, eosinophil peroxidase) are upregulated in the serum and/or skin of patients with inflammatory and pruritic skin diseases, such as chronic spontaneous urticaria or atopic dermatitis. Therefore, MRGPRX2 and its agonists might be potential biomarkers for the progression of cutaneous inflammatory diseases and the response to treatment. In addition, they may represent promising targets for prevention and treatment of signs and symptoms in patients with skin diseases or drug reactions. To assess this possibility, this review explores the role and relevance of MRGPRX2 and its activators in cutaneous inflammatory disorders and chronic pruritus.

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