IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation Regina K. Rowe, MD, PhD, David M. Pyle, MD,

Slides:

Advertisements

Similar presentations

Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut Claudia.

Advertisements

Expression of IL-9 receptor α chain on human germinal center B cells modulates IgE secretion Lama M. Fawaz, PhD, Ehssan Sharif-Askari, PhD, Oumnia Hajoui,

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu Amanda J. Reefer, MS, Kathryn.

The importance of being “pure” neutrophils

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy Yin Yao, MD, Cai-Ling.

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response Miriam Wittmann, MD, Mareike Alter, Tanja.

Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue Jolien Suurmond, MSc, Kim L.L. Habets,

Differential cytokine induction by the human skin–associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control.

Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut Claudia.

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.

Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production Mark C. Glaum, MD, PhD, Shilpi Narula, MD, Decheng Song,

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

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

Ramses Ilarraza, PhD, Yingqi Wu, Christopher D

Targeting Toll-like receptors on dendritic cells modifies the TH2 response to peanut allergens in vitro Pierre Pochard, PhD, Brian Vickery, MD, M. Cecilia.

Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis Kaori Mukai, PhD, Nicolas Gaudenzio,

Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3 Kevin O. Kisich, PhD, Charles.

Neonatal rhinovirus induces mucous metaplasia and airways hyperresponsiveness through IL-25 and type 2 innate lymphoid cells Jun Young Hong, MS, J. Kelley.

Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease Kirandeep.

Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,

Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease Kirandeep.

Targeting CD8+ T cells prevents psoriasis development

Expression of functional leukotriene B4 receptors on human airway smooth muscle cells Satoko Watanabe, BS, Akira Yamasaki, MD, PhD, Kiyoshi Hashimoto,

Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens- Johnson syndrome Tai-Ming Ko, MS, Wen-Hung Chung, MD, PhD, Chun-Yu.

Human dendritic cell subset 4 (DC4) correlates to a subset of CD14dim/−CD16++ monocytes Federica Calzetti, BS, Nicola Tamassia, PhD, Alessandra Micheletti,

Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation

Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE-dependent activation is mediated by autocrine TNF-α John T. Schroeder, PhD,

Volume 140, Issue 1, Pages e3 (January 2011)

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

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen- presenting cells that induce proallergic T cells Susanne Ebner, PhD,

David M. Pyle, BS, Victoria S. Yang, MD, Rebecca S

Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype Nicolas Gaudenzio, PhD, Camille Laurent, MD, Salvatore Valitutti,

Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy Kathryn E. Hulse, BS, Amanda J. Reefer, MS, Victor.

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.

Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid Anne-Kathrin Kienzler, MSc, Marta Rizzi, MD,

Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor Kathryn E. Hulse, PhD, Amanda J. Reefer,

Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible.

Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus–specific type 2 immune responses Stephan Traidl, Petra Kienlin,

Cigarette smoke combined with Toll-like receptor 3 signaling triggers exaggerated epithelial regulated upon activation, normal T-cell expressed and secreted/CCL5.

Chronic cat allergen exposure induces a TH2 cell–dependent IgG4 response related to low sensitization Amedee Renand, PhD, Luis D. Archila, MSc, John.

Zoulfia Allakhverdi, PhD, Michael R. Comeau, BSc, Dirk E

Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors Donald W. MacGlashan, MD, PhD,

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis Wen Hao Wu, PhD,

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired Laurence Pellerin, PhD, Jennifer Anne Jenks,

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

Decreases in human dendritic cell–dependent TH2-like responses after acute in vivo IgE neutralization John T. Schroeder, PhD, Anja P. Bieneman, BS, Kristin.

Airway epithelial cells activate TH2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin Deepti R. Nagarkar, PhD, Julie A.

Jill A. Poole, MD, Neil E. Alexis, PhD, Conrad Parks, BS, Amy K

Mammalian target of rapamycin inhibition counterbalances the inflammatory status of immune cells in patients with chronic granulomatous disease Aurélie.

Notch signaling confers antigen-presenting cell functions on mast cells Nobuhiro Nakano, PhD, Chiharu Nishiyama, PhD, Hideo Yagita, PhD, Akemi Koyanagi,

Expression of IL-9 receptor α chain on human germinal center B cells modulates IgE secretion Lama M. Fawaz, PhD, Ehssan Sharif-Askari, PhD, Oumnia Hajoui,

Josée Lamoureux, PhD, Jana Stankova, PhD, Marek Rola-Pleszczynski, MD

Expression of functional receptor activity modifying protein 1 by airway epithelial cells with dysregulation in asthma Kandace Bonner, BSc, Harsha H.

Oktay Kirak, MD, Gert Riethmüller, MD

CD23 surface density on B cells is associated with IgE levels and determines IgE- facilitated allergen uptake, as well as activation of allergen-specific.

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

Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE- independent secretion Anja P. Bieneman, BS, Kristin L. Chichester,

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

Regulation of IL-13 receptor α1 expression and signaling on human tonsillar B- lymphocyte subsets Oumnia Hajoui, PhD, Huaien Zheng, MD, PhD, Julie Guay,

IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients Antje Prasse, MD, Martin Germann,

Julie Negri, BA, S. Brandon Early, BA, John W

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

IgG4 production is confined to human IL-10–producing regulatory B cells that suppress antigen-specific immune responses Willem van de Veen, MSc, Barbara.

Ramses Ilarraza, PhD, Yingqi Wu, Christopher D

Transforming growth factor β1 increases fibronectin deposition through integrin receptor α5β1 on human airway smooth muscle Lyn M. Moir, PhD, Janette.

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

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:

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation Regina K. Rowe, MD, PhD, David M. Pyle, MD, PhD, Andrew R. Tomlinson, MD, Tinghong Lv, BS, Zheng Hu, BS, Michelle A. Gill, MD, PhD Journal of Allergy and Clinical Immunology Volume 140, Issue 1, Pages 294-298.e8 (July 2017) DOI: 10.1016/j.jaci.2016.11.035 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 IgE cross-linking inhibits virus-driven monocyte priming of TH1 cells. A, Naive CD4 T cells polarized with monocytes exposed to no virus (mock) or influenza A virus (Flu). B, Linear regression analysis was used to determine correlation between baseline monocyte FcεRI expression (x-axis) and TH1 priming capacity (% IFN-γ+ cells, y-axis) of influenza-exposed monocytes with P values and r2 values noted. N = 15. C and D, % IFN-γ+ T cells in monocyte-T-cell cocultures under IgE cross-linking conditions: (Fig 1, C) mean and (Fig 1, D) individual donor pairs. N = 15. E, Mean IFN-γ concentration in T-cell supernatants (N = 5). F, IgE cross-linking diminishes T-cell proliferation. Naive CD4 T cells labeled with VPD450 cellular dye before coculture. % divided defined as cells with lower VPD450 fluorescence compared with unstimulated T-cell controls, N = 3. Error bars represent the SEM. Pertinent P values are shown and were obtained with 2-way ANOVA analysis. G and H, Influenza A virus protein expression in monocytes at 6 and 24 hours postinfection by (Fig 1, G) flow cytometry of Flu-positive cells (NP/HA double positive) and (Fig 1, H) flow cytometry imaging at 6 hours postinfection (NP, green; HA, red). Shown is representative data from N = 3 experiments. HA, Influenza hemagglutinin; MESF, mean equivalent soluble fluorochrome; NP, influenza nucleoprotein. Error bars represent SEM, and P values represent results of 1-way ANOVA. All Material and Methods can be found in this article's Online Repository at www.jacionline.org. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IgE cross-linking inhibits virus-induced monocyte maturation and monocyte-T- cell interactions. A-C, Monocytes treated with media alone (mock) or influenza A virus (Flu) ± IgE cross-linking or IgG control antibody and stained for various cell surface markers. Representative flow cytometry (Fig 2, A) imaging analysis and (Fig 2, B) histograms for CD86 and HLA-DR staining are shown for mock and Flu only (Fig 2, C). Mean cell surface marker expression by flow cytometry analysis of the mean equivalent soluble fluorochrome (MESF, expressed as ×103 units) value was determined under the various conditions, N = 3. D, Flow cytometry imaging analysis of monocyte-T-cell interactions. Cell clusters from monocyte-T-cell cocultures stained with anti-CD3 (green), anti–HLA-DR (yellow), and nuclei (red) were visualized, 60× magnification on the Amnis ImageStream flow cytometer (Amnis, Seattle, Wash). E, Quantitation of total monocyte-T-cell clusters was performed using the IDEAS Software (Amnis) (N = 3). Error bars represent SEM, and P values represent results of 1-way ANOVA. All Material and Methods can be found in this article's Online Repository at www.jacionline.org. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 IgE cross-linking inhibits virus-driven monocyte T-cell priming and proliferation. Representative flow cytometry plots for Fig 1. Naive CD4 T cells polarized with monocytes exposed to no virus (mock) or influenza A virus (Flu) ± IgE cross-linking antibody (αIgE) or isotype IgG control. T cells were labeled with the cell proliferation dye, VPD450, before coculture. A, Zebra plots for IFN-γ expression versus VPD450 show decreased IFN-γ–positive cells in the presence of IgE cross-linking. B, Histograms show cell proliferation (measured by loss of VPD450 intensity, x-axis) of T cells stimulated with monocytes (black line) compared with unstimulated T cells in gray. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 IgE cross-linking does not alter TH2 polarization. Naive CD4 T cells polarized with monocytes exposed to no virus (mock) or influenza A virus (Flu) ± IgE cross-linking antibody (αIgE) or isotype IgG control. Graphs shown are (A) mean percentages of IL-4+ IFN-γ− cells for the indicated conditions. N = 15 donor pairs. B, Mean IL-4 concentration in monocyte-T-cell coculture supernatants. N = 5 donor pairs; error bars represent SEM, and P values represent results of 2-way ANOVA. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 IL-12 is not involved in TH1 polarization by influenza-exposed monocytes. IL-12 is a critical factor in TH1 development.E21 Neither blocking antibodies nor exogenous addition of IL-12 restored the IgE-mediated defect in TH1 differentiation. A, IL-12p70 production was measured in supernatants from monocytes treated ± IFN-γ for 18 hours followed by 24-hour incubation with media alone (mock), influenza A virus (Flu), or LPS. IL-12p70 was not detectable after influenza exposure, despite robust production under positive control conditions. Dashed line denotes the limit of detection. B, Monocyte-induced TH1 priming; mean % IFN-γ+ T cells in depicted conditions treated ± isotype control (black bars) or neutralizing IL-12 antibody (white bars). N = 3. C, % IFN-γ+ T cells ± rh IL-12. Representative data (of N = 3 experiments) is shown; error bars represent SEM and P values represent results of 1-way ANOVA. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 IgE cross-linking suppresses TH1 priming independently of TNF-α, IL-6, and IL-10. Cytokine secretion from monocyte supernatants at 18 hours after influenza virus (Flu) ± IgE cross-linking was measured for (A) TNF-α, (B) IL-6, or (C) IL-10. These were secreted by monocytes upon IgE cross-linking,7 and in the presence of both IgE cross-linking and influenza. D-F, Neutralization of these cytokines did not impact influenza-induced TH1 priming or restore inhibition by IgE cross-linking. Mean percentages of IFN-γ+ T cells in monocyte-T-cell cocultures treated with isotype controls (black bars) or neutralizing antibodies (white bars) to (Fig E4, D) TNF-α, (Fig E4, E) IL-6, or (Fig E4, F) IL-10. Representative data from N = 3 experiments are shown; error bars represent SEM, and P values represent results of 1-way ANOVA. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Model of IgE-mediated inhibition of monocyte-driven TH1 priming. Upon monocyte influenza exposure, the normal antiviral response results in phenotypic maturation and upregulation of monocyte cell surface molecules, downstream antigen presentation, and strong TCR signal culminating in TH1 differentiation. In the setting of allergic stimulation, via IgE receptor (FcεRI) engagement, virus-induced monocyte maturation is inhibited, resulting in weak TCR signal and poor TH1 differentiation. Impaired TH1 production would have significant downstream effects, including decreased antiviral cytokine secretion (eg, IFN-γ), cytotoxic CD8+ T-cell development, and antigen-specific antibody production. Journal of Allergy and Clinical Immunology 2017 140, 294-298.e8DOI: (10.1016/j.jaci.2016.11.035) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions