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Mas-related G protein–coupled receptor X2 and its activators in dermatologic allergies - 04/02/21

Doi : 10.1016/j.jaci.2020.08.027 
Helen Kühn, MSc a, , Pavel Kolkhir, MD b, c, , Magda Babina, PhD b, Miriam Düll, MD a, Stefan Frischbutter, PhD b, Jie Shen Fok, MD b, d, e, Qingqing Jiao, PhD b, f, Martin Metz, MD b, Jörg Scheffel, PhD b, Katharina Wolf, PhD a, Andreas E. Kremer, MD, PhD a, , Marcus Maurer, MD b, ,
a Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany 
b Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany 
c I.M. Sechenov First Moscow State Medical University (Sechenov University), Division of Immune-mediated Skin Diseases, Moscow, Russia 
d Department of Respiratory Medicine, Box Hill Hospital, Melbourne, Australia 
e Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia 
f Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China 

Corresponding author: Marcus Maurer, MD, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité–Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.Allergie-Centrum-CharitéDepartment of Dermatology and AllergyCharité–Universitätsmedizin BerlinCharitéplatz 1BerlinD-10117Germany

Abstract

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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Key words : MRGPRX2, MRGX2, agonists, chronic spontaneous urticaria, atopic dermatitis, substance P, neuropeptides, eosinophil granule proteins, antimicrobial peptides, pruritus, itch

Abbreviations used : AD, AMP, BAM22, C48/80, CSU, ECP, EDN, EPO, FcεRI, GPCR, hBD-2, hBD-3, HC, MBP-1, MBP-2, MC, MCT, MCTC, MRGPR, NMBA, PAF, PAMP, PTx, SCF, SP, VIP


Mappa


 This work was supported by the Russian Academic Excellence Project 5-100. A.E.K. was supported by the German Research Foundation (grants KR3618/3-1 [for 2690] and KR3618/5-1) and the Interdisciplinary Center for Clinical Research at the Friedrich Alexander University of Erlangen-Nürnberg (grants E20 and E27). M.B. was likewise supported by the German Research Foundation (grant BA3769/4-1). This work also benefitted from support of the GA2LEN network of Urticaria Centers of Reference and Excellence (UCARE, www.ga2len-ucare.com). K.W. was supported by a Bavarian Equal Opportunities Sponsorship (Realisierung von Chancengleichheit von Frauen in Forschung und Lehre–Realization Equal Opportunities for Women in Research and Teaching). P.K. was supported by a GA2LEN fellowship.
 Disclosure of potential conflict of interest: P. Kolkhir reports personal fees from Novartis and Roche outside the submitted work. Martin Metz reports personal fees from Aralez, Moxie, Novartis, Roche, Sanofi, and Uriach outside the submitted work. A. E. Kremer reports grants and/or personal fees from AbbVie, Beiersdorf, BMS, CMS, CymaBay, Eisai, Falk, Gilead, GSK, Intercept, Lilly, MSD, and Zambon outside the submitted work. M. Maurer reports grants and/or personal fees from Allakos, Amgen, Aralez, AstraZeneca, BioCryst, Blueprint, Celldex, CSL Behring, FAES, GIInnovation, Genentech, Innate Pharma, Kalvista, Kyowa Kirin, Menarini, Lilly, Leo Pharma, Moxie, MSD, Novartis, Pharming, Pharvaris, Roche, Sanofi, Shire/Takeda, ThirdHarmonicBio, UCB, and Uriach outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.


© 2020  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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