Claire Galand1, Juan Manuel Leyva-Castillo1, Juhan Yoon1, Alex Han1, Margaret S Lee1, Andrew N J McKenzie2, Michael Stassen3, Michiko K Oyoshi1, Fred D Finkelman4, Raif S Geha5. 1. Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Mass. 2. Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. 3. Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. 4. Division of Immunobiology, Cincinnati Children's Hospital Medical Center, the Department of Medicine, Cincinnati Veterans Affairs Medical Center, and the Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio. 5. Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address: raif.geha@childrens.harvard.edu.
Abstract
BACKGROUND: Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown. OBJECTIVE: We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice. METHODS: Wild-type, ST2-deficient, and MC-deficient KitW-sh/W-sh mice were epicutaneously sensitized with ovalbumin (OVA) and then challenged orally with OVA. Body temperature was measured by means of telemetry, Il33 mRNA by means of quantitative PCR, and IL-33, OVA-specific IgE, and mouse mast cell protease 1 by means of ELISA. Bone marrow-derived mast cell (BMMC) degranulation was assessed by using flow cytometry. RESULTS: Il33 mRNA expression was upregulated in tape-stripped mouse skin and scratched human skin. Tape stripping caused local and systemic IL-33 release in mice. ST2 deficiency, as well as ST2 blockade before oral challenge, significantly reduced the severity of oral anaphylaxis without affecting the systemic TH2 response to the allergen. Oral anaphylaxis was abrogated in KitW-sh/W-sh mice and restored by means of reconstitution with wild-type but not ST2-deficient BMMCs. IL-33 significantly enhanced IgE-mediated degranulation of BMMCs in vitro. CONCLUSION: IL-33 is released after mechanical skin injury, enhances IgE-mediated MC degranulation, and promotes oral anaphylaxis after epicutaneous sensitization by targeting MCs. IL-33 neutralization might be useful in treating food-induced anaphylaxis in patients with AD.
BACKGROUND: Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown. OBJECTIVE: We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice. METHODS: Wild-type, ST2-deficient, and MC-deficient KitW-sh/W-sh mice were epicutaneously sensitized with ovalbumin (OVA) and then challenged orally with OVA. Body temperature was measured by means of telemetry, Il33 mRNA by means of quantitative PCR, and IL-33, OVA-specific IgE, and mouse mast cell protease 1 by means of ELISA. Bone marrow-derived mast cell (BMMC) degranulation was assessed by using flow cytometry. RESULTS: Il33 mRNA expression was upregulated in tape-stripped mouse skin and scratched human skin. Tape stripping caused local and systemic IL-33 release in mice. ST2 deficiency, as well as ST2 blockade before oral challenge, significantly reduced the severity of oral anaphylaxis without affecting the systemic TH2 response to the allergen. Oral anaphylaxis was abrogated in KitW-sh/W-sh mice and restored by means of reconstitution with wild-type but not ST2-deficient BMMCs. IL-33 significantly enhanced IgE-mediated degranulation of BMMCs in vitro. CONCLUSION: IL-33 is released after mechanical skin injury, enhances IgE-mediated MC degranulation, and promotes oral anaphylaxis after epicutaneous sensitization by targeting MCs. IL-33 neutralization might be useful in treating food-induced anaphylaxis in patients with AD.
Authors: Päivi M Salo; Samuel J Arbes; Renee Jaramillo; Agustin Calatroni; Charles H Weir; Michelle L Sever; Jane A Hoppin; Kathryn M Rose; Andrew H Liu; Peter J Gergen; Herman E Mitchell; Darryl C Zeldin Journal: J Allergy Clin Immunol Date: 2014-02-09 Impact factor: 10.793
Authors: Lisa M Bartnikas; Michael F Gurish; Oliver T Burton; Sabine Leisten; Erin Janssen; Hans C Oettgen; Jacqueline Beaupré; Christopher N Lewis; K Frank Austen; Stephanie Schulte; Jason L Hornick; Raif S Geha; Michiko K Oyoshi Journal: J Allergy Clin Immunol Date: 2013-02 Impact factor: 10.793
Authors: Nathalie J Plundrich; Andrew R Smith; Luke B Borst; Douglas B Snider; Tobias Käser; Evan S Dellon; Anthony T Blikslager; Jack Odle; Mary Ann Lila; Scott M Laster Journal: Clin Exp Allergy Date: 2019-11-26 Impact factor: 5.018
Authors: Wendy F Davidson; Donald Y M Leung; Lisa A Beck; Cecilia M Berin; Mark Boguniewicz; William W Busse; Talal A Chatila; Raif S Geha; James E Gern; Emma Guttman-Yassky; Alan D Irvine; Brian S Kim; Heidi H Kong; Gideon Lack; Kari C Nadeau; Julie Schwaninger; Angela Simpson; Eric L Simpson; Jonathan M Spergel; Alkis Togias; Ulrich Wahn; Robert A Wood; Judith A Woodfolk; Steven F Ziegler; Marshall Plaut Journal: J Allergy Clin Immunol Date: 2019-01-09 Impact factor: 10.793
Authors: Michelle T Graham; Sandra Andorf; Jonathan M Spergel; Talal A Chatila; Kari C Nadeau Journal: Curr Allergy Asthma Rep Date: 2016-10 Impact factor: 4.806