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Due to the complexity and heterogeneity of CU and other MC diseases and mechanisms of MC activation\u2014including multiple activating receptors and ligands, diverse signaling pathways, and a menagerie of mediators\u2014strategies of MC depletion or MC silencing (i.e., inhibition of MC activation via binding of inhibitory receptors) have been developed to overcome limitations of singularly targeted agents. MC silencers, such as agonist monoclonal antibodies that engage inhibitory receptors (e.g., sialic acid\u2010binding immunoglobulin\u2010like lectin8 \u2010[Siglec\u20108] [lirentelimab\/AK002], Siglec\u20106 [AK006], and CD200R [LY3454738]), have reached preclinical and clinical stages of development. In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on\u2010 or off\u2010target, immunosuppressive adverse effects.<\/jats:p>","DOI":"10.1111\/all.15850","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T10:29:03Z","timestamp":1692700143000},"page":"37-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell\u2010mediated diseases"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4070-9976","authenticated-orcid":false,"given":"Martin","family":"Metz","sequence":"first","affiliation":[{"name":"Institute of Allergology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin (corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin)  Berlin Germany"},{"name":"Berlin Institute of Health  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5380-8132","authenticated-orcid":false,"given":"Pavel","family":"Kolkhir","sequence":"additional","affiliation":[{"name":"Institute of Allergology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin (corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin)  Berlin Germany"},{"name":"Berlin Institute of Health  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9955-385X","authenticated-orcid":false,"given":"Sabine","family":"Altrichter","sequence":"additional","affiliation":[{"name":"Institute of Allergology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin (corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin)  Berlin Germany"},{"name":"Berlin Institute of Health  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA  Berlin Germany"},{"name":"Department of Dermatology and Venerology Kepler University Hospital  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4532-1644","authenticated-orcid":false,"given":"Frank","family":"Siebenhaar","sequence":"additional","affiliation":[{"name":"Institute of Allergology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin (corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin)  Berlin Germany"},{"name":"Berlin Institute of Health  Berlin Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0620-2810","authenticated-orcid":false,"given":"Francesca","family":"Levi\u2010Schaffer","sequence":"additional","affiliation":[{"name":"Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2138-2031","authenticated-orcid":false,"given":"Bradford A.","family":"Youngblood","sequence":"additional","affiliation":[{"name":"Allakos Inc.  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