Exposure to allergen and diesel exhaust particles potentiates secondary allergen- specific memory responses, promoting asthma susceptibility Eric B. Brandt,

Slides:

Advertisements

Similar presentations

Background The association between air pollution, including traffic related air pollution (TRAP), and increased risk for respiratory disease is now widely.

Advertisements

Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses Katrien C. De Grove, MSc, Sharen Provoost,

Exposure to allergen and diesel exhaust particles potentiates secondary allergen- specific memory responses, promoting asthma susceptibility Eric B. Brandt,

Surface availability of beta-glucans is critical determinant of host immune response to Cladosporium cladosporioides Rachael A. Mintz-Cole, PhD, Eric.

Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A

Glucagon-like peptide 1 receptor signaling attenuates respiratory syncytial virus– induced type 2 responses and immunopathology Melissa H. Bloodworth,

Thymic stromal lymphopoietin signaling in CD4+ T cells is required for TH2 memory Qun Wang, PhD, Jianguang Du, PhD, Jingjing Zhu, MSc, Xiaowei Yang, MSc,

Weiguo Chen, PhD, Umasundari Sivaprasad, PhD, Aaron M

The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF- like (BATF), regulates lymphocyte- and mast cell–driven immune.

The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF- like (BATF), regulates lymphocyte- and mast cell–driven immune.

Umasundari Sivaprasad, PhD, David J. Askew, PhD, Mark B

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

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

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

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

Lack of autophagy induces steroid-resistant airway inflammation

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,

Elisabeth Roesler, MSc, Richard Weiss, PhD, Esther E

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

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

Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,

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

Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function Yafang Tang, BSc, Shou Ping Guan, BSc, Benson.

Β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses Zhonghua Zhang, MD, Jocelyn.

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

Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33 Susana Castanhinha, MD, Rebekah Sherburn, MSc, Simone Walker,

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

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

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

Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A.

Dawn C. Newcomb, PhD, Madison G

Prime role of IL-17A in neutrophilia and airway smooth muscle contraction in a house dust mite–induced allergic asthma model Julie Chesné, PhD, Faouzi.

Early-life chlamydial lung infection enhances allergic airways disease through age- dependent differences in immunopathology Jay C. Horvat, PhD, Malcolm.

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

Experimental gastrointestinal allergy enhances pulmonary responses to specific and unrelated allergens Eric B. Brandt, PhD, Troy A. Scribner, MD, Hiroko.

Frank Kirstein, PhD, Natalie E

Inhibition of house dust mite–induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment Adam Collison,

Decreased T-cell receptor signaling through CARD11 differentially compromises forkhead box protein 3–positive regulatory versus TH2 effector cells to.

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

T-cell immunoglobulin and mucin domain 1 deficiency eliminates airway hyperreactivity triggered by the recognition of airway cell death Hye Young Kim,

Prostaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells Zbigniew Zasłona, PhD, Katsuhide.

Takao Kobayashi, PhD, Koji Iijima, PhD, Alexander L

Surface availability of beta-glucans is critical determinant of host immune response to Cladosporium cladosporioides Rachael A. Mintz-Cole, PhD, Eric.

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.

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,

Jethe O. F. Nunes, PhD, Juliana de Souza Apostolico, MSc, David A. G

Regulation of allergic airway inflammation by class I–restricted allergen presentation and CD8 T-cell infiltration James W. Wells, PhD, Christopher J.

Janus kinase 1/3 signaling pathways are key initiators of TH2 differentiation and lung allergic responses Shigeru Ashino, PhD, Katsuyuki Takeda, MD,

Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses Katrien C. De Grove, MSc, Sharen Provoost,

Prostaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells Zbigniew Zasłona, PhD, Katsuhide.

Does reduced zona pellucida binding protein 2 (ZPBP2) expression on chromosome 17q21 protect against asthma? Marina Miller, MD, PhD, Christine Vuong,

Role of B cells in TH cell responses in a mouse model of asthma

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

Sarita Sehra, PhD, Weiguo Yao, PhD, Evelyn T. Nguyen, MS, Nicole L

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

IL-17A enhances IL-13 activity by enhancing IL-13–induced signal transducer and activator of transcription 6 activation Sara L. Hall, MS, Theresa Baker,

Effects of established allergen sensitization on immune and airway responses after secondary allergen sensitization Katharina Blumchen, MD, Kerstin Gerhold,

Staphylococcal enterotoxin A–activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation Wei-ping Zeng,

Susceptibility to allergic lung disease regulated by recall responses of dual-receptor memory T cells∗ Mark A. Aronica, MD, Shadi Swaidani, MS, Yan H.

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

Duy Pham, PhD, Sarita Sehra, PhD, Xin Sun, PhD, Mark H. Kaplan, PhD

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

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

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

Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis Christopher D.

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

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

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

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:

Exposure to allergen and diesel exhaust particles potentiates secondary allergen- specific memory responses, promoting asthma susceptibility Eric B. Brandt, PhD, Jocelyn M. Biagini Myers, PhD, Thomas H. Acciani, BS, Patrick H. Ryan, PhD, Umasundari Sivaprasad, PhD, Brandy Ruff, BS, Grace K. LeMasters, PhD, David I. Bernstein, MD, James E. Lockey, MD, Timothy D. LeCras, PhD, Gurjit K. Khurana Hershey, MD, PhD Journal of Allergy and Clinical Immunology Volume 136, Issue 2, Pages 295-303.e7 (August 2015) DOI: 10.1016/j.jaci.2014.11.043 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 DEP exacerbation of HDM-induced airway TH2 responses returns to baseline within a month. A, Protocol: BALB/c mice were exposed intratracheally (i.t.) to 50 μL of saline, DEP (150 μg), and/or HDM (10 μg) 3 times a week over a 3-week period. B-D, Mice were killed 1, 8, and 30 days after the last exposure, and total BALF cell levels (Fig 2, B), as well as BALF neutrophil (Fig 2, C) and eosinophil (Fig 2, D) counts, were assessed (3 separate experiments with a total of n = 11-16 mice per group [day 1], n = 7-12 mice per group [day 8], and n = 5-8 mice per group [day 30]). E and F, BALF levels of IL-4 (Fig 1, E) and IL-13 (Fig 1, F) were assessed by using the multiplex assay and IL-13/IL-13Rα2 ELISA, respectively. G, Airway resistance to methacholine challenges was assessed by using flexiVent. H, Representative photomicrographs of CLCA3-stained lung sections. Scale = 100 μm. D, DEP, H, HDM; n.s., not significant; S, saline. *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Persistent increase in lung effector/memory T-cell counts after HDM plus DEP exposure. Characterization of lung T cells 1, 8, and 30 days after the last exposure to saline (S), DEP (D), HDM (H), or HDM plus DEP (HD) by using fluorescence-activated cell sorting. A, Total lung cells. B and C, CD4+CD44+CD62L− T cells (Fig 2, B) and CD69 expression (Fig 2, C) by effector/memory T cells (2 separate experiments with 2-8 mice per group). *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Increased presence of memory TH2 and TH17 cells in the lungs 1 month after coexposure to HDM and DEP. A, TH1, TH2, and TH17 lung cells were identified by means of fluorescence-activated cell sorting as CD4+ T cells expressing IFN-γ, IL-13, and IL-17A, respectively, after ex vivo stimulation with phorbol 12-myristate 13-acetate/ionomycin for 4 hours. B and C, Percentage of IL-13+IL-17+ double producers among CD4+CD44+ T cells (Fig 3, B) and IL-7 receptor mean fluorescence intensity (CD127 [MFI]; Fig 3, C) on naive and CD4+CD44+ T cells. Fig 3, C, IL-4 and IL-17A were detected by means of ELISA in supernatants of lung cells stimulated with HDM (30 μg/mL) for 5 days (n = 4-8 mice per group). *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test (P values were calculated by using the t test). D, DEP, H, HDM; n.s., not significant; S, saline. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Primary exposure to HDM and DEP potentiates secondary HDM-specific responses in vivo. A, Protocol: A single intratracheal (i.t.) challenge with either saline or 10 μg of HDM was performed 7 weeks after the last exposure to either saline, DEP, HDM, or HDM plus DEP. B, AHR was assessed 40 hours after HDM recall challenge (2-way ANOVA). C, HDM-specific IgG1 and IgE levels 7 weeks after primary exposure. D-F, Total BALF cell (Fig 4, D), neutrophil (Fig 4, E), and eosinophil (Fig 4, F) counts (n = 4-10 mice per group). *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test. D, DEP, H, HDM; n.s., not significant; S, saline. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Increased presence of HDM-specific memory cells 7 weeks after coexposure to HDM plus DEP results in increased TH2/TH17 responses on secondary HDM challenge. A-D, BALF levels of eotaxin-1 (Fig 5, A), TH2 cytokines (IL-4, IL-5, and IL-13; Fig 5, B), the TH1 cytokine IFN-γ (Fig 5, C), and the TH17-related cytokine IL6 (Fig 5, D; n = 8-10 mice per group). E, TH2 and TH17 lungs cells were identified by means of fluorescence-activated cell sorting as CD4+CD44+ T cells expressing IL-13 and IL-17A, respectively, after ex vivo stimulation with phorbol 12-myristate 13-acetate/ionomycin for 4 hours. F, Percentage of IL-13+IL-17+ double-producing CD4+CD44+ T cells (n = 4-6 mice per group). **P < .01 and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test. D, DEP, H, HDM; n.s., not significant; S, saline. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Exposure to high birth ECAT levels contributed to significantly higher asthma prevalence at age 7 years. A, Children exposed to high ECAT levels are more likely to be sensitized to an aeroallergen at age 2 years compared with children exposed to low ECAT levels (35% vs 47%). #P = .011. B and C, Children exposed to high ECAT levels (top quartile) that were sensitized to HDM (Fig 6, B) or had positive SPT responses (Fig 6, C) to any of the 15 aeroallergens tested in the first 4 years of life were significantly more likely to have asthma by age 7 years (P = .045 and P = .022, respectively). All P values were calculated by using χ2 tests and SAS software; numbers of asthmatic patients/total cases in each group are presented above asthma prevalence bars. D, Proposed model. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 HDM-induced eosinophil cytokine levels return to baseline, whereas DEP-induced neutrophil chemokine levels remain increased 8 days after exposure. A, Protocol: BALB/c mice were exposed intratracheally (i.t.) to saline, DEP (150 μg), and/or HDM (10 μg) 3 times a week over a 3-week period. Mice were killed 1 and 8 days after the last exposure. B and C, BALF levels of the eosinophil-related cytokines IL-5 and eotaxin-1, as well as BALF levels of the neutrophil chemokines CXCL1 and CXCL5, were assessed by using the multiplex assay (n = 6-10 mice per group). *P < .05, **P < .01, and ***P < .001, 1-way ANOVA. D, DEP, H, HDM; S, saline. D, Representative photomicrographs of lung section stained with periodic acid–Schiff. Scale = 100 μm. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Increased presence of HDM-specific memory cells in the lungs 6 to 7 weeks after coexposure to HDM and DEP. A, IL-13+ and IL-17+ lung cells were identified by means of fluorescence-activated cell sorting among CD3+CD4+CD44+ T cells after ex vivo stimulation with phorbol 12-myristate 13-acetate/ionomycin for 4 hours. B, IL-4, IL-13, and IL-17A were detected by using ELISAs in supernatants of lung cells stimulated with HDM (30 μg/mL) for 5 days (n = 4-7 mice per group). *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 DEPs persist in lung phagocytic cells over 3 months after a single DEP exposure. BALB/c mice were exposed intratracheally (it) to 50 μL of saline or DEPs (150 μg) once and killed 1 day or 1, 3, 6, or 12 weeks after exposure (n = 4 mice per group). The amount of DEPs present in alveolar macrophages was estimated by using a scale of 0 to 4. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Increased presence of HDM-specific cells in draining lymph nodes and spleens 6 to 7 weeks after coexposures to HDM and DEPs. A, Lymph node cell numbers 1, 30, and 45 days after exposure to saline, DEP, HDM, or both. B, Photomicrograph of lymph nodes 45 days after the last HDM plus DEP exposure. C and D, IL-4 and IL-17A levels in supernatants of lymph node cells (n = 2-6 mice per group; Fig E4, C) or spleen cells (n = 3-7 mice per group; Fig E4, D) stimulated with HDM (30 μg/mL) for 6 days. E, IL-4 and IL-17A secreted by highly enriched CD4+ T cells from spleen cells stimulated with plate bound anti-CD3 for 3 days (n = 3-7). *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test; P values were calculated by using the t test. D, DEP, H, HDM; n.s., not significant; S, saline. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Early-life exposure to DEPs and HDM potentiates HDM-specific recall responses in adult mice. A, Protocol: Postnatal day 3 pups were exposed intranasally (i.n.) for 9 days to either saline, DEP (6 mg/kg), HDM (2 mg/kg), or HDM plus DEP and then rested for 4 weeks before all groups were rechallenged with HDM. B, Airway resistance was measured by using flexiVent 24 hours after the last HDM rechallenge. C, BALF eosinophil numbers and eotaxin-1 levels. D and E, BALF TH2 cytokines (IL-4, IL-5, and IL-13; Fig E5, D) and TH17-related cytokines (IL-6 and IL-17A; Fig E5, E) were assessed by using the multiplex assay (n = 5-6 mice per group). F, HDM-specific serum IgG1 levels. *P < .05, **P < .01, and ***P < .001, 1-way ANOVA with the Bonferroni multiple comparison test. D, DEP, H, HDM; n.s., not significant; S, saline. Journal of Allergy and Clinical Immunology 2015 136, 295-303.e7DOI: (10.1016/j.jaci.2014.11.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions