Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases.

Autor: Metz M; Institute of Allergology, Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, Germany., Kolkhir P; Institute of Allergology, Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, Germany., Altrichter S; Institute of Allergology, Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, Germany.; Department of Dermatology and Venerology, Kepler University Hospital, Linz, Austria., Siebenhaar F; Institute of Allergology, Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, Germany., Levi-Schaffer F; Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Youngblood BA; Allakos Inc., San Carlos, California, USA., Church MK; Institute of Allergology, Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, Germany., Maurer M; Institute of Allergology, Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, Germany.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 Jan; Vol. 79 (1), pp. 37-51. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1111/all.15850
Abstrakt: 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.
(© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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