Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33 Chloé Michaudel, PhD, Claire Mackowiak, MSc, Isabelle.

Slides:

Advertisements

Similar presentations

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease Ana Paula Moreira, PhD, Karen A.

Advertisements

Tze Khee Chan, BSc, Xin Yi Loh, BSc, Hong Yong Peh, BSc, W. N

Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein Chih-Hsing Hung, MD, Li-Chen Chen, MD, Zhongjian Zhang, PhD, Bhabadeb.

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma Kyung S. Lee, MS, Sun M. Jin,

Weiguo Chen, MD, PhD, Yasuhiro Tabata, MD, PhD, Aaron M

Robert J. Snelgrove, PhD, Lisa G

Tze Khee Chan, BSc, Xin Yi Loh, BSc, Hong Yong Peh, BSc, W. N

Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation

Interferon response factor 3 is essential for house dust mite–induced airway allergy Thomas Marichal, DVM, Denis Bedoret, DVM, PhD, Claire Mesnil, DVM,

Frank Kirstein, PhD, Natalie E

Lack of autophagy induces steroid-resistant airway inflammation

Nazanin Farhadi, MSc, Laura Lambert, BA, Chiara Triulzi, PhD, Peter J

The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter Jeremy A. Hirota,

Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival Jyoti Balhara, MSc, Lianyu Shan,

The parasitic 68-mer peptide FhHDM-1 inhibits mixed granulocytic inflammation and airway hyperreactivity in experimental asthma Akane Tanaka, BSc, Venkata.

Autocrine hemokinin-1 functions as an endogenous adjuvant for IgE-mediated mast cell inflammatory responses Tina L. Sumpter, PhD, Chin H. Ho, MD, Anna.

Protein corona–mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses Limei Shen, PhD, Stefan Tenzer, PhD, Wiebke.

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

Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH2- inducing allergen exposures Matthew J. Gold, BSc, Frann Antignano,

IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin Robert J. Salmond, PhD, Ananda S. Mirchandani,

Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation Si-Yen Liu, PhD, Wei-Zhi Wang,

Environmental changes could enhance the biological effect of Hop J pollens on human airway epithelial cells Seung Ihm Lee, PhD, Le Duy Pham, MD, Yoo.

Allergic airway disease is unaffected by the absence of IL-4Rα–dependent alternatively activated macrophages Natalie E. Nieuwenhuizen, PhD, Frank Kirstein,

Lung dendritic cells induce TH17 cells that produce TH2 cytokines, express GATA-3, and promote airway inflammation Marianne Raymond, PhD, Vu Quang Van,

Proinflammatory role of epithelial cell–derived exosomes in allergic airway inflammation Ankur Kulshreshtha, MTech, Tanveer Ahmad, MSc, Anurag Agrawal,

Signaling through FcRγ-associated receptors on dendritic cells drives IL-33–dependent TH2-type responses Melissa Y. Tjota, BA, Cara L. Hrusch, PhD, Kelly.

CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling Jennifer Kearley, PhD, Douglas S. Robinson,

Aeroallergen-induced IL-33 predisposes to respiratory virus–induced asthma by dampening antiviral immunity Jason P. Lynch, PhD, Rhiannon B. Werder, B.

Frank Kirstein, PhD, Natalie E

Overexpression of sirtuin 6 suppresses allergic airway inflammation through deacetylation of GATA3 Hyun-Young Jang, PhD, Suna Gu, MS, Sang-Myeong Lee,

Requirements for allergen-induced airway inflammation and hyperreactivity in CD4- deficient and CD4-sufficient HLA-DQ transgenic mice Svetlana P. Chapoval,

A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell–dependent murine model of allergic asthma

Jamie Rosen, Angelo Landriscina, Allison Kutner, Brandon L

Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis Chisa Nakashima, MD, Atsushi Otsuka, MD, PhD, Akihiko.

Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms Wenru Su, MD,

G-quadruplex DNA targeting alters class-switch recombination in B cells and attenuates allergic inflammation Zeinab Dalloul, MSc, Pauline Chenuet, MSc,

Exaggerated IL-17 response to epicutaneous sensitization mediates airway inflammation in the absence of IL-4 and IL-13 Rui He, MD, PhD, Hye Young Kim,

Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33 Chloé Michaudel, PhD, Claire Mackowiak, MSc, Isabelle.

Prophylactic and therapeutic inhibition of allergic airway inflammation by probiotic Escherichia coli O83 Christian Zwicker, MSc, Priya Sarate, MSc,

CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease Helen Martin, MS,

Nerve growth factor induces type III collagen production in chronic allergic airway inflammation Ayşe Kılıç, MSc, Sanchaita Sriwal Sonar, PhD, Ali Oender.

Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation Md Ashik Ullah, MPharm, Joana A. Revez,

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

The cardiomyocyte protein αT-catenin contributes to asthma through regulating pulmonary vein inflammation Stephen Sai Folmsbee, G.R. Scott Budinger,

Receptor-interacting protein kinase 3 controls keratinocyte activation in a necroptosis- independent manner and promotes psoriatic dermatitis in mice

Src homology 2 domain–containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung Sun-Young Oh, PhD,

MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation Kristina.

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge

CD4+ T lymphocytes mediate acute pulmonary ischemia–reperfusion injury

Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity Iris Bellinghausen, PhD, Sebastian.

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease Ana Paula Moreira, PhD, Karen A.

13-Hydroxy-linoleic acid induces airway hyperresponsiveness to histamine and methacholine in guinea pigs in vivo Paul A.J. Henricks, PhDa, Ferdi Engels,

Biju Thomas, MD, Robert Anthony Hirst, PhD, Mina H

IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation Kentaro Takahashi, MD, Koichi.

Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: Role of eosinophils, IL-5, eotaxin, and IL-13 Seok-Yong.

Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma

MicroRNA-155 is essential for TH2-mediated allergen-induced eosinophilic inflammation in the lung Carina Malmhäll, BSc, Sahar Alawieh, BSc, You Lu, PhD,

Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways Ryszard Dworski, MD, PhD, Hans-Uwe Simon, MD, PhD, Aimee Hoskins,

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

Therapeutic efficacy of an anti–IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma Felix R. Shardonofsky, MD,

The extra domain A of fibronectin is essential for allergen-induced airway fibrosis and hyperresponsiveness in mice Martin Kohan, MSc, Andres F. Muro,

Aeroallergen-induced IL-33 predisposes to respiratory virus–induced asthma by dampening antiviral immunity Jason P. Lynch, PhD, Rhiannon B. Werder, B.

Junqing Cui, PhD, Stephen Pazdziorko, Joy S

Local treatment with IL-12 is an effective inhibitor of airway hyperresponsiveness and lung eosinophilia after airway challenge in sensitized mice Jürgen.

Corticosteroids enhance CD8+ T cell–mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1 Hiroshi Ohnishi,

Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge

TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice Susumu Nakae, PhD, Carolina Lunderius, PhD,

Presentation transcript:

Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33 Chloé Michaudel, PhD, Claire Mackowiak, MSc, Isabelle Maillet, BSc, Louis Fauconnier, MSc, Cezmi A. Akdis, MD, Milena Sokolowska, MD, PhD, Anita Dreher, MSc, Hern-Tze Tina Tan, PhD, Valérie F. Quesniaux, PhD, Bernhard Ryffel, MD, PhD, Dieudonnée Togbe, PhD Journal of Allergy and Clinical Immunology Volume 142, Issue 3, Pages 942-958 (September 2018) DOI: 10.1016/j.jaci.2017.11.044 Copyright © 2018 The Authors Terms and Conditions

Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10 Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 1 Epithelial damage, chemokine production, and cell death in BALF on ozone exposure. A, Time course of epithelial cell recruitment and total protein, IL-6, and chemokine (CXCL1, MIP-2, and MCP-1) levels in BALF. B, Neutrophil counts, MPO levels, macrophage counts (both interstitial and alveolar), and TIMP-1 and MMP-9 levels in BALF. C, Total ROS expression and cell death (7-AAD+) in BALF. D, Histologic analysis (hematoxylin and eosin staining) of lung tissue for epithelial damage score. Scale bar = 100 μm. Arrows indicate desquamation. Data are from 3 independent experiments. Values are expressed as means ± SEMs with 5 to 6 mice per group. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 2 IL-33 expression in the lung after ozone exposure. A and B, Time course of pulmonary IL-33 protein expression by using Luminex (Fig 2, A) and cleavage forms by using Western blotting at 24 hours in WT (Fig 2, B). C, Immunofluorescence staining of IL-33 24 hours after ozone exposure, frequency, and mean fluorescence intensity (MFI) of IL-33+ cells in WT mice. Scale bar = 100 μm. DAPI, 4′-6-Diamidino-2-phenylindole dihydrochloride. D and E, Absolute numbers of IL 33–citrine+ cells in BALF and lung tissue on ozone exposure using IL-33 citrine reporter mice at 24 hours. Data are representative of 2 independent experiments. Values are expressed as means ± SEMs with 5 to 6 mice per group. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 3 Ozone-induced lung inflammation is enhanced in Il33– and ST2-deficient mice 24 hours after ozone exposure. A-C, Total cells, neutrophils, and macrophages (Fig 3, A); CXCL1, MPO, and LCN-2; Fig 2, B); and MMP-9, TIMP-1, and AREG (Fig 3, C) in BALF of WT, ST2−/−, and Il33−/− mice. D, Histologic analysis (hematoxylin and eosin staining) of lung tissue and cell infiltration in the peribronchial area and epithelial damage scores in ST2−/− or Il33−/− mice. Scale bar = 100 μm. Arrows indicate cell infiltration. Data are pooled from 4 experiments. Values are expressed as means ± SEMs with 4 to 6 mice per group. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 3 Ozone-induced lung inflammation is enhanced in Il33– and ST2-deficient mice 24 hours after ozone exposure. A-C, Total cells, neutrophils, and macrophages (Fig 3, A); CXCL1, MPO, and LCN-2; Fig 2, B); and MMP-9, TIMP-1, and AREG (Fig 3, C) in BALF of WT, ST2−/−, and Il33−/− mice. D, Histologic analysis (hematoxylin and eosin staining) of lung tissue and cell infiltration in the peribronchial area and epithelial damage scores in ST2−/− or Il33−/− mice. Scale bar = 100 μm. Arrows indicate cell infiltration. Data are pooled from 4 experiments. Values are expressed as means ± SEMs with 4 to 6 mice per group. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 4 ST2 antibody neutralization enhanced inflammatory cell recruitment 24 hours after ozone exposure in WT mice. A, Anti-ST2 or isotype control antibody treatment study scheme. B-D, Total cells, neutrophils, and macrophages (Fig 4, B); CXCL1, MPO, and LCN-2; Fig 4, C); and MMP-9, TIMP-1, and AREG (Fig 4, D) in BALF from WT mice. E, Histologic analysis (hematoxylin and eosin staining) with cell infiltration in the peribronchial area and epithelial damage scores from the lungs of WT mice treated with ST2 neutralizing antibody. Scale bar = 100 μm. Arrows indicate desquamation. Semiquantitative scores are shown. Experiments are pooled of 2 experiments and repeated twice. Values are expressed as means ± SEMs with 5 to 6 mice per group. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 4 ST2 antibody neutralization enhanced inflammatory cell recruitment 24 hours after ozone exposure in WT mice. A, Anti-ST2 or isotype control antibody treatment study scheme. B-D, Total cells, neutrophils, and macrophages (Fig 4, B); CXCL1, MPO, and LCN-2; Fig 4, C); and MMP-9, TIMP-1, and AREG (Fig 4, D) in BALF from WT mice. E, Histologic analysis (hematoxylin and eosin staining) with cell infiltration in the peribronchial area and epithelial damage scores from the lungs of WT mice treated with ST2 neutralizing antibody. Scale bar = 100 μm. Arrows indicate desquamation. Semiquantitative scores are shown. Experiments are pooled of 2 experiments and repeated twice. Values are expressed as means ± SEMs with 5 to 6 mice per group. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 5 Neutrophil depletion attenuates inflammation. GR-1 antibody administration study scheme (A); effect of GR-1 depletion on total cells, neutrophils, macrophages, desquamation (epithelial cell), and cell death (7-AAD+; B); and airways hyperresponsiveness to increasing doses of methacholine (C). Data are pooled from 2 experiments. Values are expressed as means ± SEMs with 5 to 6 mice for air and ozone. i.p., Intraperitoneal. **P < .01 and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 6 Ozone-induced disruption of the epithelial barrier is mediated by IL-33/ST2 signaling at 24 hours. Histologic analysis (hematoxylin and eosin staining) of lung sections from WT and ST2−/− mice. Scale bar = 100 μm. A-D, Desquamation (arrows) and injury score (Fig 6, A), epithelial desquamation (Fig 6, B), epithelial barrier permeability with Evans Blue leakage at 24 hours into BALF (Fig 6, C), and airway resistance (Fig 6, D) in WT and ST2−/− mice. E, E-cadherin expression in BALF from rIL-33–treated WT, ST2−/−, and Il33−/− mice 24 hours after exposure. Experimental data are pooled from 2 experiments. Values are expressed as means ± SEMs with 4 to 6 mice per group. F, ZO-1 expression after ozone exposure at 24 hours in WT and ST2−/− mice. Representative images of 1 experiment are shown in the upper panel. Quantification of ZO-1 expression, as depicted in the lower panel, is shown as mean fluorescence intensity from 3 independent experiments. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions

Fig 6 Ozone-induced disruption of the epithelial barrier is mediated by IL-33/ST2 signaling at 24 hours. Histologic analysis (hematoxylin and eosin staining) of lung sections from WT and ST2−/− mice. Scale bar = 100 μm. A-D, Desquamation (arrows) and injury score (Fig 6, A), epithelial desquamation (Fig 6, B), epithelial barrier permeability with Evans Blue leakage at 24 hours into BALF (Fig 6, C), and airway resistance (Fig 6, D) in WT and ST2−/− mice. E, E-cadherin expression in BALF from rIL-33–treated WT, ST2−/−, and Il33−/− mice 24 hours after exposure. Experimental data are pooled from 2 experiments. Values are expressed as means ± SEMs with 4 to 6 mice per group. F, ZO-1 expression after ozone exposure at 24 hours in WT and ST2−/− mice. Representative images of 1 experiment are shown in the upper panel. Quantification of ZO-1 expression, as depicted in the lower panel, is shown as mean fluorescence intensity from 3 independent experiments. *P < .05, **P < .01, ***P < .001, and ****P < .0001. Journal of Allergy and Clinical Immunology 2018 142, 942-958DOI: (10.1016/j.jaci.2017.11.044) Copyright © 2018 The Authors Terms and Conditions