title: Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy.
abstract: Experimental IgE-mediated food allergy depends on intestinal anaphylaxis driven by interleukin-9 (IL-9). However, the primary cellular source of IL-9 and the mechanisms underlying the susceptibility to food-induced intestinal anaphylaxis remain unclear. Herein, we have reported the identification of multifunctional IL-9-producing mucosal mast cells (MMC9s) that can secrete prodigious amounts of IL-9 and IL-13 in response to IL-33, and mast cell protease-1 (MCPt-1) in response to antigen and IgE complex crosslinking, respectively. Repeated intragastric antigen challenge induced MMC9 development that required T cells, IL-4, and STAT6 transcription factor, but not IL-9 signals. Mice ablated of MMC9 induction failed to develop intestinal mastocytosis, which resulted in decreased food allergy symptoms that could be restored by adoptively transferred MMC9s. Finally, atopic patients that developed food allergy displayed increased intestinal expression of Il9- and MC-specific transcripts. Thus, the induction of MMC9s is a pivotal step to acquire the susceptibility to IgE-mediated food allergy.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Jee-Boong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kartashov
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Mugge
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Abonia
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Artem
authors.initials: A
authors.lastname: Barski
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Medicine, Cincinnati Veterans Affairs Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hogan
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: yui_hsi.wang@cchmc.org.
authors.forename: Yui-Hsi
authors.initials: YH
authors.lastname: Wang
mesh_terms: D019264:Adoptive Transfer; D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D053818:Chymases / Q000096:biosynthesis / Q000235:genetics; D003967:Diarrhea / Q000209:etiology / Q000276:immunology; D004198:Disease Susceptibility; D004386:Duodenum / Q000276:immunology / Q000473:pathology; D005512:Food Hypersensitivity / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications; D007073:Immunoglobulin E / Q000276:immunology*; D016906:Interleukin-9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D008415:Mastocytosis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000502:physiology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016906:Interleukin-9; D007378:Interleukins; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin; D053818:Chymases; C509230:Mcpt1 protein, mouse