Role of TGF-β in anti-rhinovirus immune responses in asthmatic patients Carina Bielor, Nina Sopel, PhD, Anja Maier, MSc, Ashley Blau, Himanshu Sharma,

Slides:

Advertisements

Similar presentations

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

Advertisements

Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo Jan Gutermuth, MD, Mayte Bewersdorff,

Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial Eve Hornsby, PhD, Paul E. Pfeffer,

Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma Chun-Yu Lo, MD, Charalambos Michaeloudes,

Allergen endotoxins induce T-cell–dependent and non–IgE-mediated nasal hypersensitivity in mice Naruhito Iwasaki, MD, Kazufumi Matsushita, PhD, Ayumi.

The effects of upper respiratory infection on T-cell proliferation and steroid sensitivity of asthmatics Elcio O. Vianna, MD, PhD, Jay Westcott, PhD,

Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,

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

Let-7 microRNA–mediated regulation of IL-13 and allergic airway inflammation Manish Kumar, MSc, Tanveer Ahmad, MSc, Amit Sharma, PhD, Ulaganathan Mabalirajan,

Epigenetic regulation of established human type 1 versus type 2 cytokine responses Ruey-Chyi Su, PhD, Allan B. Becker, MD, Anita L. Kozyrskyj, PhD, Kent.

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

Sytze de Roock, PhD, Arie J

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis Eva Gros, MSc, Susanne Petzold,

Elena Goleva, PhD, Leisa P. Jackson, BS, Melanie Gleason, PA, Donald Y

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

Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids Kittipong Maneechotesuwan, MD, PhD, Sirinya.

Increased expression of nuclear factor of activated T cells 1 drives IL-9–mediated allergic asthma Sonja Koch, PhD, Anna Graser, PhD, Hooman Mirzakhani,

Ramses Ilarraza, PhD, Yingqi Wu, Christopher D

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

FOXP3+ CD4 T-cell maturity and responses to microbial stimulation alter with age and associate with early-life gut colonization Sophia Björkander, Maria.

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

Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin Mohan S. Maddur, DVM, Janakiraman Vani,

Differential control of TH1 versus TH2 cell responses by the combination of low-dose steroids with β2-adrenergic agonists Elena Goleva, PhD, Annegret.

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

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.

Glucocorticoids promote intrinsic human TH17 differentiation

Dawn C. Newcomb, PhD, Madison G

Effects of lidocaine on regulatory T cells in atopic dermatitis

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,

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

The innate antiviral response upregulates IL-13 receptor α2 in bronchial fibroblasts Gemma Campbell-Harding, PhD, Hannah Sawkins, BSc, Nicole Bedke, PhD,

Jovana Maric, MSc, Avinash Ravindran, MSc, Luca Mazzurana, MSc, Åsa K

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

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype.

Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin Sucai Liu, PhD,

Bcl2-like protein 12 plays a critical role in development of airway allergy through inducing aberrant TH2 polarization Zhi-Qiang Liu, MD, PhD, Ying Feng,

Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution Hari K. Somineni, MS, Xue Zhang,

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

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA GATA3-AS1 Huan Zhang, MD, PhD, Colm E. Nestor, PhD, Shuli Zhao, PhD,

Sandra Hellberg, MSc, Ratnesh B

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

Fibronectin is a TH1-specific molecule in human subjects

Inhibition of angiogenesis by IL-32: Possible role in asthma

Activin A is an acute allergen-responsive cytokine and provides a link to TGF-β– mediated airway remodeling in asthma Christian Karagiannidis, MD, Gabriele.

Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus Julie.

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,

Fibronectin is a TH1-specific molecule in human subjects

Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution Hari K. Somineni, MS, Xue Zhang,

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

Matthew J. Loza, PhD, Susan Foster, PhD, Stephen P

Sputum inflammatory cells from patients with allergic rhinitis and asthma have decreased inflammasome gene expression Willie June Brickey, PhD, Neil.

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

Rhinovirus infection interferes with induction of tolerance to aeroantigens through OX40 ligand, thymic stromal lymphopoietin, and IL-33 Amit K. Mehta,

Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma

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

Stelios Psarras, PhD, Eleni Volonaki, MD, Chrysanthi L

Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects Hiroyuki Fujita, MD, PhD, Maciej Chalubinski, MD, PhD,

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

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

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

Nrf2 activation by sulforaphane restores the age-related decrease of TH1 immunity: Role of dendritic cells Hyon-Jeen Kim, PhD, Berenice Barajas, BS,

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

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.

Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids Kittipong Maneechotesuwan, MD, PhD, Sirinya.

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

Presentation transcript:

Role of TGF-β in anti-rhinovirus immune responses in asthmatic patients Carina Bielor, Nina Sopel, PhD, Anja Maier, MSc, Ashley Blau, Himanshu Sharma, MSc, Tytti Vuorinen, MD, PhD, Bettina Kroß, MSc, Susanne Mittler, Anna Graser, PhD, Stephanie Mousset, MSc, Volker O. Melichar, MD, Alexander Kiefer, MD, Theodor Zimmermann, MD, Rebekka Springel, Corinna Holzinger, Sonja Trump, Stella Taka, PhD, Nikolaos G. Papadopoulos, MD, Scott T. Weiss, MD, Susetta Finotto, PhD Journal of Allergy and Clinical Immunology Volume 140, Issue 1, Pages 283-286.e10 (July 2017) DOI: 10.1016/j.jaci.2016.10.049 Copyright © 2016 The Authors Terms and Conditions

Fig 1 PBMCs from asthmatic children exposed to RV1b in vitro upregulated IDO, PDL1, and LAP3. A, Experimental design for RNA arrays of PBMCs cultured in the presence or absence of rhinovirus (RV). B-E, Heat maps for asthmatic (Fig 1, B and C) and control (Fig 1, D and E) children and a differential expression analysis of the regulated genes are shown (asthma: n = 7, control: n = 5). Journal of Allergy and Clinical Immunology 2017 140, 283-286.e10DOI: (10.1016/j.jaci.2016.10.049) Copyright © 2016 The Authors Terms and Conditions

Fig 2 Rhinovirus (RV) inhibits TGF-β release from PBMCs isolated from healthy and asthmatic children. A, TGF-β1 release from PBMCs of asthmatic and nonasthmatic children with or without in vitro rhinovirus infection analyzed by means of ELISA (n = 26-32 children per group, B0+F4). B-E, Relative mRNA expression of TGFB (Fig 2, B; n = 12-20), TGFBRII (Fig 2, C; n =3-6), FOXP3 (Fig 2, D; n = 19-31), and RORC (Fig 2, E; n = 19-31) in asthmatic and nonasthmatic children with or without in vitro rhinovirus infection (B0+F4) analyzed by means of real-time PCR. F-I, Correlation of RORC and FOXP3 mRNA expression in untreated and in vitro–infected PBMCs from asthmatic and nonasthmatic children. J and K, Relative TBX21 (Fig 2, J; n = 10-22) or IL6 (Fig 2, K; n = 10-27) mRNA expression from PBMCs in asthmatic and healthy children with or without in vitro rhinovirus treatment analyzed by using real-time PCR. The Student t test was used to calculate statistical significance. *P ≤ .05, **P ≤ .01, and ***P ≤ .001. Results are expressed as means ± SEMs. Journal of Allergy and Clinical Immunology 2017 140, 283-286.e10DOI: (10.1016/j.jaci.2016.10.049) Copyright © 2016 The Authors Terms and Conditions

Fig E1 MRNA expression of IDO in PBMCs. A, IDO mRNA expression in PBMCs from asthmatic (A) and nonasthmatic (CN) children with (+RV) or without (−RV) in vitro rhinovirus treatment. B, PBMCs from healthy volunteers were in vitro incubated with different concentrations of dexamethasone (Dex), 10−6 mol/L and 10−8 mol/L, and IDO expression was determined by using qPCR. *P ≤ .05 and **P ≤ .01. Journal of Allergy and Clinical Immunology 2017 140, 283-286.e10DOI: (10.1016/j.jaci.2016.10.049) Copyright © 2016 The Authors Terms and Conditions

Fig E2 Rhinovirus induces TC1 cells in a murine model of asthma. A, Experimental design. i.n., Intranasal; i.p., intraperitoneal. B, CD8+IFN-γ+ cells were analyzed in total lung cells by using flow cytometry. A dot plot is shown for each group (n = 4-5 mice per group). *P ≤ .05, **P ≤ .01, and ***P ≤ .001. Journal of Allergy and Clinical Immunology 2017 140, 283-286.e10DOI: (10.1016/j.jaci.2016.10.049) Copyright © 2016 The Authors Terms and Conditions

Fig E3 TGF-β treatment of rhinovirus-infected cells reduces T-bet expression in CD4+ T cells in a murine model of asthma. A, Experimental design. i.n., Intranasal; i.p., intraperitoneal. B, Ido mRNA expression was detected in total lung cells from naive mice cultured with TGF-β after in vitro treatment with rhinovirus or untreated (n = 4). C, CD4+T-bet+ cells were analyzed in total lung cells from naive or OVA-treated mice by using flow cytometry. Exemplary dot plots are depicted for each group analyzed (n = 4-5 mice per group). *P ≤ .05 and **P ≤ .01. Journal of Allergy and Clinical Immunology 2017 140, 283-286.e10DOI: (10.1016/j.jaci.2016.10.049) Copyright © 2016 The Authors Terms and Conditions