title: IL-9-producing cells in the development of IgE-mediated food allergy.
abstract: Food allergy is a harmful immune reaction driven by uncontrolled type 2 immune responses. Considerable evidence demonstrates the key roles of mast cells, IgE, and TH2 cytokines in mediating food allergy. However, this evidence provides limited insight into why only some, rather than all, food allergic individuals are prone to develop life-threatening anaphylaxis. Clinical observations suggest that patients sensitized to food through the skin early in life may later develop severe food allergies. Aberrant epidermal thymic stromal lymphopoietin and interleukin (IL) 33 production and genetic predisposition can initiate an allergic immune response mediated by dendritic cells and CD4+TH2 cells in inflamed skin. After allergic sensitization, intestinal IL-25 and food ingestion enhance concerted interactions between type 2 innate lymphoid cells (ILC2s) and CD4+TH2 cells, which perpetuate allergic reactions from the skin to the gut. IL-4 and cross-linking of antigen/IgE/FcεR complexes induce emigrated mast cell progenitors to develop into the multi-functional IL-9-producing mucosal mast cells, which produce prodigious amounts of IL-9 and mast cell mediators to drive intestinal mastocytosis in an autocrine loop. ILC2s and TH9 cells may also serve as alternative cellular sources of IL-9 to augment the amplification of intestinal mastocytosis, which is the key cellular checkpoint in developing systemic anaphylaxis. These findings provide a plausible view of how food allergy develops and progresses in a stepwise manner and that atopic signals, dietary allergen ingestion, and inflammatory cues are fundamental in promoting life-threatening anaphylaxis. This information will aid in improving diagnosis and developing more effective therapies for food allergy-triggered anaphylaxis.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Burnet Avenue, Cincinnati, OH, 45229, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Shik
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Burnet Avenue, Cincinnati, OH, 45229, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Tomar
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, 34141, South Korea.
authors.forename: Jee-Boong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Nationwide Children's Hospital, Columbus, 43205, USA.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Burnet Avenue, Cincinnati, OH, 45229, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Burnet Avenue, Cincinnati, OH, 45229, USA. yui_hsi.wang@cchmc.org.
authors.forename: Yui-Hsi
authors.initials: YH
authors.lastname: Wang
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D005502:Food / Q000009:adverse effects; D005512:Food Hypersensitivity / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism*; D007108:Immune Tolerance / Q000276:immunology; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D016906:Interleukin-9 / Q000096:biosynthesis / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D016906:Interleukin-9; D007073:Immunoglobulin E