title: Immunoglobulin E signal inhibition during allergen ingestion leads to reversal of established food allergy and induction of regulatory T cells.
abstract: Immunoglobulin E (IgE) antibodies are known for triggering immediate hypersensitivity reactions such as food anaphylaxis. In this study, we tested whether they might additionally function to amplify nascent antibody and T helper 2 (Th2) cell-mediated responses to ingested proteins and whether blocking IgE would modify sensitization. By using mice harboring a disinhibited form of the IL-4 receptor, we developed an adjuvant-free model of peanut allergy. Mast cells and IgE were required for induction of antibody and Th2-cell-mediated responses to peanut ingestion and they impaired regulatory T (Treg) cell induction. Mast-cell-targeted genetic deletion of the FcεRI signaling kinase Syk or Syk blockade also prevented peanut sensitization. In mice with established allergy, Syk blockade facilitated desensitization and induction of Treg cells, which suppressed allergy when transferred to naive recipients. Our study suggests a key role for IgE in driving Th2 cell and IgE responses while suppressing Treg cells in food allergy.
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Burton
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Magali
authors.initials: M
authors.lastname: Noval Rivas
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Zhou
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Logsdon
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Alanna R
authors.initials: AR
authors.lastname: Darling
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Koleoglou
authors.affiliation: Institut für Immunologie, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.affiliation: Respiratory and Immunology, Merck Research Laboratories, Boston, MA 02115, USA.
authors.forename: Hani
authors.initials: H
authors.lastname: Houshyar
authors.affiliation: Respiratory and Immunology, Merck Research Laboratories, Boston, MA 02115, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crackower
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Talal A
authors.initials: TA
authors.lastname: Chatila
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: hans.oettgen@childrens.harvard.edu.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021183:Peanut Hypersensitivity / Q000235:genetics / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse