Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa Stephanie A. Leonard, MD, Gustavo Martos, PhD, Wei Wang, MD, Anna.

Slides:

Advertisements

Similar presentations

Immunotherapy for Food Allergy: Are We There Yet?

Advertisements

Therapeutic reversal of food allergen sensitivity by mature retinoic acid–differentiated dendritic cell induction of LAG3+CD49b−Foxp3− regulatory T cells

Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice Laurent L. Reber, PhD, Thomas Marichal, DVM, PhD, Kaori Mukai,

IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling Clinton B. Mathias, PhD, Suejy.

Advances in food allergy in 2015

Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity

Antigen-driven basophil activation is indicative of early Necator americanus infection in IgE-seronegative patients Franco H. Falcone, PhD, Gary Telford,

Jay A. Lieberman, MD, Faith R. Huang, MD, Hugh A

Maternal allergy increases susceptibility to offspring allergy in association with TH2- biased epigenetic alterations in a mouse model of peanut allergy

Allergy prevention starts before conception: Maternofetal transfer of tolerance protects against the development of asthma Tobias Polte, PhD, Christian.

A novel allergen-specific therapy for allergy using CD40-silenced dendritic cells Motohiko Suzuki, MD, PhD, Xiufen Zheng, PhD, Xusheng Zhang, MD, PhD,

Allergic sensitization can be induced via multiple physiologic routes in an adjuvant- dependent manner David Dunkin, MD, M. Cecilia Berin, PhD, Lloyd.

Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE- mediated hypersensitivity Oliver T. Burton, PhD, Stephanie L. Logsdon,

Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis Paul J. Bryce, PhD, Rustom Falahati, PhD,

Frank Kirstein, PhD, Natalie E

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring Phoebe K. Richgels, MS, Amnah.

Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived memory T cells in an allergy model Roman Karwot, PhD, Joachim H. Maxeiner,

Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis Lisa M. Bartnikas, MD, Michael F. Gurish,

Allergen-induced IgE-dependent gut inflammation in a human PBMC–engrafted murine model of allergy Benno Weigmann, PhD, Nadja Schughart, MSc, Christian.

Matthew C. Tunis, BSc, Wojciech Dawicki, PhD, Kaitlyn R

IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs Chien-Chang Chen, PhD, Takao Kobayashi, PhD, Koji Iijima,

Activated glycoprotein A repetitions predominant (GARP)–expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice

Dawn C. Newcomb, PhD, Madison G

Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy Kamal D. Srivastava, PhD, Alyssa Siefert,

Pharmacologic inhibition of Notch signaling suppresses food antigen–induced mucosal mast cell hyperplasia Asuka Honjo, MD, Nobuhiro Nakano, PhD, Susumu.

Forkhead box protein 3 demethylation is associated with tolerance induction in peanut- induced intestinal allergy Meiqin Wang, MD, PhD, Ivana V. Yang,

Differential roles for the IL-9/IL-9 receptor α-chain pathway in systemic and oral antigen–induced anaphylaxis Heather Osterfeld, BSc, Richard Ahrens,

Oliver T. Burton, PhD, Jaciel M. Tamayo, PhD, Amanda J

Frank Kirstein, PhD, Natalie E

Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model Lucie Mondoulet, PhD, Vincent Dioszeghy, PhD, Emilie Puteaux,

Miriam Wittmann, MD, Jana Zeitvogel, Dong Wang, MD, Thomas Werfel, MD

Ellen Mueller Fox, PhD, Marina N

Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin–basophil axis Mario Noti,

Food allergy herbal formula 2 protection against peanut anaphylactic reaction is via inhibition of mast cells and basophils Ying Song, MD, Chunfeng Qu,

Rapid polyclonal desensitization with antibodies to IgE and FcεRIα

Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8+ T cells Kamal D. Srivastava,

A fusion protein of flagellin and ovalbumin suppresses the TH2 response and prevents murine intestinal allergy Stefan Schülke, PhD, Manja Burggraf, MSc,

IL-2–inducible T-cell kinase modulates TH2-mediated allergic airway inflammation by suppressing IFN-γ in naive CD4+ T cells Arun K. Kannan, MS, Nisebita.

IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells Claire Galand, PhD, Juan Manuel Leyva-Castillo, PhD, Juhan.

Iván López-Expósito, PhD, Ying Song, MD, Kirsi M

IgE-class–specific immunosuppression in offspring by administration of anti-IgE to pregnant mice Hideaki Morita, MD, PhD, Masato Tamari, MD, PhD, Masako.

Mechanisms underlying differential food allergy response to heated egg

Role of hyaluronan and hyaluronan-binding proteins in human asthma

Concurrent blockade of platelet-activating factor and histamine prevents life-threatening peanut-induced anaphylactic reactions Katherine Arias, BHSc,

Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway Meiqin Wang, MD, PhD, Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

A novel allergen-specific therapy with CD40-silenced B cells and dendritic cells Motohiko Suzuki, MD, PhD, Makoto Yokota, MD, PhD, Yoshihisa Nakamura,

Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge Elke O. Luger, PhD, Verena Fokuhl, MSc, Michael Wegmann, PhD, Melanie.

Rapid desensitization of mice with anti-FcγRIIb/FcγRIII mAb safely prevents IgG- mediated anaphylaxis Marat V. Khodoun, PhD, Zeynep Yesim Kucuk, MD, Richard.

Orally administered TGF-β is biologically active in the intestinal mucosa and enhances oral tolerance Takashi Ando, MD, PhD, Kyosuke Hatsushika, MD,

Oral administration of a synthetic agonist of Toll-like receptor 9 potently modulates peanut-induced allergy in mice Fu-Gang Zhu, PhD, Ekambar R. Kandimalla,

Ana Belén Blázquez, Lloyd Mayer, M. Cecilia Berin Gastroenterology

Kirthana Ganeshan, BS, Colleen V

Allergen-specific sublingual immunotherapy is dose and duration dependent in a murine allergic rhinitis model Soichi Tofukuji, PhD, Kazufumi Katayama,

Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice Jianing Li, MS, Yu Wang,

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

Eric B. Brandt, PhD, Ariel Munitz, PhD, Tatyana Orekov, MS, Melissa K

Ellen Mueller Fox, PhD, Marina N

The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis Meiqin Wang, MD, PhD, Julita Ramirez, DVM, PhD,

DNA methylation of TH1/TH2 cytokine genes affects sensitization and progress of experimental asthma Stephanie Brand, PhD, Dörthe Andrea Kesper, PhD,

Jenny Seltmann, PhD, Lennart M

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity James N. Francis, PhD, Louisa.

Dietary baked egg accelerates resolution of egg allergy in children

Eric B. Brandt, PhD, Melissa K. Mingler, MS, Michelle D

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production Monika Majewska-Szczepanik, PhD,

Placental transfer of allergen-specific IgG but not IgE from a specific immunotherapy– treated mother Sabine Flicker, PhD, Katharina Marth, MD, Heinz.

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis Jennifer K. Mulligan, PhD, Whitney Nagel,

Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Madhan Masilamani, PhD, John Wei, BA, Shiven Bhatt,

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

IL-2–inducible T-cell kinase modulates TH2-mediated allergic airway inflammation by suppressing IFN-γ in naive CD4+ T cells Arun K. Kannan, MS, Nisebita.

Presentation transcript:

Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa Stephanie A. Leonard, MD, Gustavo Martos, PhD, Wei Wang, MD, Anna Nowak-Węgrzyn, MD, M. Cecilia Berin, PhD Journal of Allergy and Clinical Immunology Volume 129, Issue 6, Pages 1579-1587.e1 (June 2012) DOI: 10.1016/j.jaci.2012.04.009 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 OIT results in desensitization but not tolerance to OVA (A) or OM (B). OVA- and OM-sensitized mice were administered OIT, or left untreated (control). Mice were orally challenged (on OIT), and again 2 weeks after the discontinuation of OIT (off OIT). Thirty minutes after the challenge, body temperature was measured (left) and a clinical score was assigned (right). ns, Not significant. Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Immunologic changes associated with OIT in mice. Mice were orally sensitized to OVA, followed by the administration of egg white OIT. A, OVA-specific IgE, IgG1, IgG2a, and IgA levels measured in serum obtained on the last day of OIT. B, Cytokine secretion from OVA-restimulated spleen cells obtained 2 weeks after OIT discontinuation. *P < .05. Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 OIT decreases gastrointestinal epithelial barrier function. Mice were orally sensitized to OVA, followed by the administration of egg white OIT on days 0 to 14. On day 15, segments of jejunum were removed and mounted in Ussing chambers. Transmural resistance was measured at baseline (left), and luminal-to-serosal transport of FITC-dextran was measured over a 90-minute period (right). FITC, Fluorescein isothiocyanate. **P < .01. Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 High-dose OIT is required for clinical protection against OVA-induced anaphylaxis in sensitized mice. OVA-sensitized mice were administered high-dose or low-dose fresh egg white OIT on days 0 to 14, or left untreated (control). Mice were orally challenged on day 15. Thirty minutes after the challenge, body temperature was measured (left) and a clinical score was assigned (right). Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Extensively heated OM protects mice against anaphylaxis. OM-sensitized mice were administered native or heated-OM OIT on days 0 to 14, or left untreated (control). Mice were orally challenged with native OM on day 15. Thirty minutes after the challenge, body temperature was measured (left) and a clinical score was assigned (right). Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Clinical protection is localized to the gastrointestinal tract. OVA-sensitized mice received egg white OIT on days 0 to 14. On day 15: A, Peripheral blood basophil activation. *P < .05 versus naive. B, Peritoneal mast cell activation. n = 5 per group. **P < .01 versus unstimulated. C, Body temperature before and after the challenge. D, Body temperature after graded intraperitoneal dose challenge to OVA. MFI, Median fluorescence intensity. ∗∗∗P < .001 versus naive. Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 OIT significantly alters intestinal gene expression. A, Jejunal gene expression of pancreatic lipase (Pnlp), trypsin 4 (Try4), trypsin 5 (Try5), and GP2 was measured by PCR. B, Expression of Pnlp and Try4 in proximal and mid duodenum, jejunum, and proximal and distal ileum. Expression of Pnlp and Try4 in isolated intestinal epithelial cells (IEC) compared with full-thickness intestine (right). CT, Cholera toxin; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A, Basophil activation as measured by CD200R. Whole blood was incubated in plates coated with anti-IgE (R35-72) or rat IgG1 as isotype control, or with 10 μg of OVA. Cells were stained, and basophils identified as CD3neg CD19neg CD49bpos IgEpos. Left: CD200R expression on basophils incubated with media alone (shaded histogram), isotype control (solid line), or anti-IgE (dotted line). Right: Basophils from naive, OVA-sensitized but untreated (control), or OVA-sensitized and OIT-treated (OIT) mice, incubated with media alone (shaded histogram) or OVA (solid line). Histograms are representative of 3 individual experiments, with each experiment using pooled blood from 3 to 4 mice per group. B, Peritoneal mast cell activation as measured by LAMP-1. Top panel: Peritoneal cells were harvested from naive mice and incubated in plates coated with anti-IgE (R35-72) or rat IgG1 as isotype control. Cells were harvested after 30, 60, or 120 minutes, and LAMP-1 detected on c-kitpos FcεRIpos cells. Data from 3 individual mice are shown in the graph on the right. Bottom panel: Peritoneal cells were harvested from naive, control, or OIT-treated mice and cultured with OVA (10 μg) or media alone for 60 minutes. LAMP-1 was then detected as above. Histograms are representative of 5 mice per group. MFI, Median fluorescence intensity. Journal of Allergy and Clinical Immunology 2012 129, 1579-1587.e1DOI: (10.1016/j.jaci.2012.04.009) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions