Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases.
allergic
inflammation
inflammatory
mast cell
urticaria
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
22 Aug 2023
22 Aug 2023
Historique:
revised:
21
06
2023
received:
24
04
2023
accepted:
29
07
2023
medline:
22
8
2023
pubmed:
22
8
2023
entrez:
22
8
2023
Statut:
aheadofprint
Résumé
Chronic urticaria (CU) is a mast cell (MC)-dependent disease with limited therapeutic options. Current management strategies are directed at inhibiting IgE-mediated activation of MCs and antagonizing effects of released mediators. Due to the complexity and heterogeneity of CU and other MC diseases and mechanisms of MC activation-including multiple activating receptors and ligands, diverse signaling pathways, and a menagerie of mediators-strategies 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-binding immunoglobulin-like lectin8 -[Siglec-8] [lirentelimab/AK002], Siglec-6 [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- or off-target, immunosuppressive adverse effects.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Allakos, Inc.
Informations de copyright
© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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US National Library of Medicine. A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis. 2021. Accessed January 23, 2023. https://clinicaltrials.gov/ct2/show/study/NCT03750643?term=LY3454738&draw=2&rank=2
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