Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway Isabelle Dupin,

Slides:

Advertisements

Similar presentations

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy Erik Wambre, PhD, Jonathan.

Advertisements

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease Merja T. Augustin, MD, Jorma Kokkonen, MD,

The natural history of soy allergy

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease Merja T. Augustin, MD, Jorma Kokkonen, MD,

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity Laetitia Everaere, PhD, Saliha Ait-Yahia, PhD, Olivier Molendi-Coste,

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease Nicola Cotugno, MD, Andrea Finocchi,

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit.

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

Fibrocyte localization to the airway smooth muscle is a feature of asthma Ruth Saunders, PhD, Salman Siddiqui, MRCP, Davinder Kaur, PhD, Camille Doe,

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease Nicola Cotugno, MD, Andrea Finocchi,

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

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

Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection

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

Immunologic defects in 22q11.2 deletion syndrome

Frank Kirstein, PhD, Natalie E

Distinct endotypes of steroid-resistant asthma characterized by IL-17Ahigh and IFN- γhigh immunophenotypes: Potential benefits of calcitriol Emma S. Chambers,

Type 2 innate lymphoid cells in induced sputum from children with severe asthma Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.

Selective dysfunction of p53 for mitochondrial biogenesis induces cellular proliferation in bronchial smooth muscle from asthmatic patients Thomas Trian,

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

CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation Clarisa M. Buckner, PhD, Susan Moir, PhD, Lela Kardava,

Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells Shuo Li, PhD, Hideaki Morita, MD, PhD, Beate Rückert, Sci Tec, Tadech.

Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL- 23 receptor signaling and IL-17A production in patients with severe.

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

Susceptibility to influenza virus infection of bronchial biopsies in asthma Ben Nicholas, PhD, Sarah Dudley, PhD, Kamran Tariq, MD, Peter Howarth, DM,

Frank Kirstein, PhD, Natalie E

Lieuwe D. Bos, MSc, PhD, Peter J. Sterk, MD, PhD, Stephen J

Tacrolimus and TGF-β act synergistically on the generation of Langerhans cells Bartlomiej Kwiek, MD, Wen-Ming Peng, MSc, Jean-Pierre Allam, MD, Andrzej.

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

Allergen-induced, eotaxin-rich, proangiogenic bone marrow progenitors: A blood-borne cellular envoy for lung eosinophilia Kewal Asosingh, PhD, Jodi D.

Jerome A. Sigua, MD, Becky Buelow, MD, Dorothy S

Differential expression of functional chemokine receptors on human blood and lung group 2 innate lymphoid cells Cathryn A. Weston, PhD, Batika M.J. Rana,

Airway epithelial cells from asthmatic children differentially express proremodeling factors Jesus M. Lopez-Guisa, PhD, Claire Powers, BA, Daniele File,

Katherine G. MacDonald, BSc, Nicholas A. J

Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients Dan Davini, BA, Fouzia Naeem, MD,

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.

Allison K. Martin, BS, Douglas G. Mack, PhD, Michael T

Β2 integrins rather than β1 integrins mediate Alternaria-induced group 2 innate lymphoid cell trafficking to the lung Maya R. Karta, PhD, Peter S. Rosenthal,

A thymic stromal lymphopoietin–responsive dendritic cell subset mediates allergic responses in the upper airway mucosa Guro R. Melum, MD, Lorant Farkas,

Benjamin T. Prince, MD, Msci, Ashley L. Devonshire, MD, MPH, Kristin A

Floor Weerkamp, MSc, Edwin F. E. de Haas, BSc, Brigitta A. E

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

Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development

Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin- exacerbated respiratory disease Jacqueline J. Eastman, MD, Kellen.

Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression Kathryn E. Hulse, PhD, James E.

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

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations Jonatan Leffler, PhD, Anya C. Jones,

Kerstin Bauermeister, MSc, Barbara K

Individual IL-3 priming is crucial for consistent in vitro activation of donor basophils in patients with chronic urticaria Thomas Gentinetta, MSc, Tatjana.

Toll-like receptor 2–positive and Toll-like receptor 4–positive cells in adenoids of children exposed to passive smoking Antonio Ricci, MD, M. Antonietta.

Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma Chaoyu.

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy Erik Wambre, PhD, Jonathan.

CC chemokine receptors CCR1 and CCR4 are expressed on airway mast cells in allergic asthma Kawa Amin, PhD, Christer Janson, MD, PhD, Ilkka Harvima, MD,

Allergen-specific CD8+ T cells in peanut-allergic individuals

Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5− TH2 responses Calman Prussin, MD, Joohee Lee,

Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti–IL-5 antibody SCH55700 Yae-Jean.

Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis Eva Gros, MSc, Caroline Bussmann,

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

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study

Karl J. Staples, PhD, Timothy S. C. Hinks, MB BS, Jon A

Diagnostic testing and interpretation of tests for autoimmunity

Pulmonary chemokines and their receptors differentiate children with asthma and chronic cough Dominik Hartl, MD, Matthias Griese, MD, Thomas Nicolai,

Human newborn B cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus Jop Jans, MD, Matthew Pettengill, PhD,

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease Jaclyn Smith, MD, PhD, Emily Owen, MPhil, John Earis, MD,

Natural history of cow’s milk allergy

Alexander S. Kim, MD, Taylor A. Doherty, MD, Maya R

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

Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis David W. Morris, MD, Emily M. Stucke, BA, Lisa.

Presentation transcript:

Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway Isabelle Dupin, PhD, Benoit Allard, PhD, Annaig Ozier, MD, PhD, Elise Maurat, MSc, Olga Ousova, PhD, Eva Delbrel, MSc, Thomas Trian, PhD, Hoang-Nam Bui, MD, Claire Dromer, MD, Olivier Guisset, MD, Elodie Blanchard, MD, Gilles Hilbert, MD, PhD, Frédéric Vargas, MD, PhD, Matthieu Thumerel, MD, Roger Marthan, MD, PhD, Pierre-Olivier Girodet, MD, PhD, Patrick Berger, MD, PhD Journal of Allergy and Clinical Immunology Volume 137, Issue 4, Pages 1036-1042.e7 (April 2016) DOI: 10.1016/j.jaci.2015.08.043 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Study design. Numbers of patients who were included and had their fibrocyte counts quantified. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Increased blood fibrocyte counts during COPD exacerbation. A and B, Circulating fibrocytes (CD45+Col1+ cells) expressed as a percentage of PBMCs (Fig 2, A) and counts in blood (Fig 2, B) from control subjects (Cont, n = 40), patients with nonexacerbating COPD (NEx, n = 9), and patients with exacerbating COPD (V1, n = 54) are shown. *P < .05, **P < .01, and ***P < .001, nonparametric Kruskal-Wallis test. C and D, CD45+CD34+Col1+ cells expressed as a percentages of PBMCs (Fig 2, C) and counts in blood (Fig 2, D) from control subjects (Cont, n = 29), patients with nonexacerbating COPD (NEx, n = 8), and patients with exacerbating COPD (V1, n = 41). *P < .05, nonparametric Kruskal-Wallis test. Fig 2, A-D, Medians are represented as horizontal lines. E and F, Comparison of fibrocytes (CD45+Col1+ cells) in patients with exacerbating COPD at the time of exacerbation (V1) and 2 months after exacerbation resolution (V2). **P < .01, Wilcoxon matched pairs test. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Consequences of increased fibrocyte percentages on survival and lung function in patients with COPD. A, Kaplan-Meier survival analysis comparing patients with exacerbating COPD and greater than 28% CD45+Col1+ cells among PBMCs measured at the time of exacerbation (n = 6; black curve) with patients with less than 28% CD45+Col1+ cells among PBMCs (n = 36; gray curve). B-D, Relationships between FEV1 (Fig 3, B), FVC (Fig 3, C), Pao2 (Fig 3, D), and the percentage of CD45+Col1+ cells in PBMCs in patients with exacerbating COPD at V2. Correlation coefficient (r) and significance level (P value) were obtained by using nonparametric Spearman analysis. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Analysis of fibrocyte marker expression by means of flow cytometry. Expression of CXCR4 (A and B), CCR2 (C and D), CCR3 (E and F), and CCR7 (G and H) in fibrocytes from control subjects (Cont) and patients with exacerbating COPD (V1). Fibrocytes are CD45+Col1+ cells. Results were expressed as percentages of PBMCs (Fig 4, A, C, E, and G) and counts in blood (Fig 4, B, D, F, and H). *P < .05 and **P < .01, Mann-Whitney tests. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Analysis of fibrocyte chemotaxis. A, Migration of fibrocytes from control subjects (n = 8, gray bars) and patients with exacerbating COPD (n = 6, black bars) in response to plasma from patients with exacerbating COPD in the presence or absence of 25 μg/mL plerixafor. *P < .05, paired t test. B, Plasma CXCL12-α levels in individual subjects. Cont, Control subjects; NE, patients with nonexacerbating COPD; V1, patients with exacerbating COPD during an AECOPD; V2, patients with exacerbating COPD in the stable state. C, Migration of fibrocytes from control subjects (n = 8, gray lines) and patients with exacerbating COPD (n = 5, black lines) in response to CXCL12. **P < .01, 2-way ANOVA with Bonferroni tests. D, Migration of fibrocytes from control subjects (n = 5) and patients with exacerbating COPD (n = 7) in response to CXCL12 in the presence or absence of 25 μg/mL plerixafor. *P < .05, paired t test. Results were expressed as means ± SEMs (Fig 5, A, C, and D) or with symbols indicating individual subject values and horizontal gray lines representing medians (Fig 5, B). Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Identification of fibrocytes by using flow cytometry and phase-contrast microscopy. Representative dot plots of flow cytometry for fibrocyte quantification from a patient with COPD exacerbation. A, Total NANT cell population selected on unstained cells. B, Isotype control for CD45 set on unstained cells. C, Positive population for CD45. D, Isotype control for collagen-1 set on a CD45-gated population. E, Positive population for both CD45 and collagen-1. FITC, Fluorescein isothiocyanate; FSC-A, forward scatter; SSC-A, side scatter. F, Representative image of cultured blood fibrocytes taken with a phase-contrast microscope, showing their morphology as spindle-shaped adherent cells. Bar = 20 μm. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Percentage of CD45+Col1+ cells among PBMCs of patients with exacerbating COPD at V2 with 1 or no unscheduled visits (n = 15) or with 2 or more unscheduled visits (n = 16) the year before V1. Medians are represented as gray horizontal lines. *P < .05, Mann-Whitney test. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 A, Migration of fibrocytes from control subjects (n = 3, gray bars) and patients with exacerbating COPD (n = 6, black bars) in response to plasma of patients with exacerbating COPD in the presence or absence of 3.8 μg/mL SB 328437 (paired t test). B, Plasma CCL11 levels in individual subjects. Cont, Control subjects; NE, patients with nonexacerbating COPD; V1, patients with exacerbating COPD during an AECOPD; V2, patients with exacerbating COPD in the stable state. C, Migration of fibrocytes from control subjects (n = 4, gray lines) and patients with exacerbating COPD (n = 6, black lines) in response to CCL11. D, Migration of fibrocytes from control subjects (n = 4) and patients with exacerbating COPD (n = 5) in response to CCL11 in the presence or absence of 3.8 μg/mL SB 328437. P < .001, paired t test. Results are expressed as means ± SEMs (Fig E3, A, C, and D) or with symbols indicating individual subject values and horizontal gray lines representing medians (Fig E3, B). ***P < .001. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Individual CXCL12-β plasma concentrations. Cont, Control subjects; NEx, patients with nonexacerbating COPD; V1, patients with exacerbating COPD during an AECOPD; V2, patients with exacerbating COPD in the stable state. Symbols indicate individual subjects, and horizontal gray lines represent medians. Journal of Allergy and Clinical Immunology 2016 137, 1036-1042.e7DOI: (10.1016/j.jaci.2015.08.043) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions