title: Exon skipping of FcεRIβ eliminates expression of the high-affinity IgE receptor in mast cells with therapeutic potential for allergy.
abstract: Allergic diseases are driven by activation of mast cells and release of mediators in response to IgE-directed antigens. However, there are no drugs currently available that can specifically down-regulate mast cell function in vivo when chronically administered. Here, we describe an innovative approach for targeting mast cells in vitro and in vivo using antisense oligonucleotide-mediated exon skipping of the β-subunit of the high-affinity IgE receptor (FcεRIβ) to eliminate surface high-affinity IgE receptor (FcεRI) expression and function, rendering mast cells unresponsive to IgE-mediated activation. As FcεRIβ expression is restricted to mast cells and basophils, this approach would selectively target these cell types. Given the success of exon skipping in clinical trials to treat genetic diseases such as Duchenne muscular dystrophy, we propose that exon skipping of FcεRIβ is a potential approach for mast cell-specific treatment of allergic diseases.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607; gpcruse@ncsu.edu.|Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Glenn
authors.initials: G
authors.lastname: Cruse
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Avanti
authors.initials: A
authors.lastname: Desai
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
authors.forename: Greer K
authors.initials: GK
authors.lastname: Arthur
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumer
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beaven
authors.affiliation: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D017449:Dermatitis, Allergic Contact / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics; D012326:RNA Splicing / Q000187:drug effects*; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C521907:Fc-epsilon receptor I beta-chain, mouse; D016376:Oligonucleotides, Antisense; D017455:Receptors, IgE; D002118:Calcium
keywords: IgE receptor; allergy; dermatitis; mast cell; oligonucleotides