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Airway Wall Expression of OX40/OX40L and Interleukin-4 in Asthma

Journal Article · · Chest
 [1];  [2];  [2];  [3];  [3];  [2]
  1. University of Leicester (United Kingdom); DOE/OSTI
  2. University of Leicester (United Kingdom)
  3. University of Leicester (United Kingdom); AstraZeneca, Charnwood, Loughborough (United Kingdom)
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The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T helper 2 polarization. We sought to examine OX40/ OX40L and interleukin (IL)-4 expression in asthma across severities. Bronchial biopsies were obtained from 27 subjects with asthma (mild Global Initiative for Asthma [GINA] 1 [n = 10], moderate GINA 2-3 [n = 7], and severe GINA 4-5 [n = 10]) and 13 healthy controls. The number of OX40+, OX40L+, IL-4+ , and IL-4 receptor a (IL-4Rα)+ cells in the lamina propria and airway smooth muscle (ASM) bundle and the intensity of IL-4Rα+ expression by the ASM were assessed. The number of OX40+, OX40L+, and IL-4+ cells in the lamina propria and OX40+ and IL-4+ cells in the ASM bundle was significantly increased in subjects with mild asthma, but not in those with moderate or severe asthma, compared with healthy controls. In the subjects with asthma, OX40/OX40L expression was positively correlated with the number of eosinophils and IL-4+ cells in the lamina propria. The number of IL-4Rα+ cells in the lamina propria was significantly increased in moderate-to-severe disease, but not in mild asthma, compared with controls. IL-4R a expression by the ASM bundle was not different among groups. OX40/OX40L expression is increased in the bronchial submucosa in mild asthma, but not in moderate-to-severe disease, and is related to the degree of tissue eosinophilia and IL-4 expression. Whether these costimulatory molecules have a role as targets for asthma requires further investigation.
Research Organization:
University of Leicester (United Kingdom)
Sponsoring Organization:
AstraZeneca; MedImmune
OSTI ID:
1627924
Journal Information:
Chest, Journal Name: Chest Journal Issue: 4 Vol. 137; ISSN 0012-3692
Publisher:
American College of Chest Physicians, Elsevier
Country of Publication:
United States
Language:
English

References (32)

Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses journal June 2009
Interleukin-13 in asthma pathogenesis journal December 2004
Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell–mediated allergic inflammation journal August 2007
Sputum and bronchial submucosal IL-13 expression in asthma and eosinophilic bronchitis journal November 2004
In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation journal December 2007
Fibrocyte localization to the airway smooth muscle is a feature of asthma journal February 2009
Tumour necrosis factor (TNF ) as a novel therapeutic target in symptomatic corticosteroid dependent asthma journal December 2005
The use of induced sputum to investigate airway inflammation journal June 1997
Mucosal inflammation in severe glucocorticoid-dependent asthma journal June 1999
Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells journal January 2000
Master switches of T-cell activation and differentiation journal January 2007
OX40 (CD134) Controls Memory T Helper 2 Cells that Drive Lung Inflammation journal July 2003
Immunohistochemistry on Resin Sections: A Comparison of Resin Embedding Techniques for Small Mucosal Biopsies journal January 1993
Increased sputum and bronchial biopsy IL-13 expression in severe asthma journal March 2008
Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation journal October 2002
Innate immune activation in neutrophilic asthma and bronchiectasis journal March 2007
Asthma-Related Environmental Fungus, Alternaria , Activates Dendritic Cells and Produces Potent Th2 Adjuvant Activity journal February 2009
Efficacy of soluble IL-4 receptor for the treatment of adults with asthma journal June 2001
Mast-Cell Infiltration of Airway Smooth Muscle in Asthma journal May 2002
Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma journal April 2003
Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsìveness, and the late asthmatic response journal December 2000
Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies journal October 2007
Eosinophilic bronchitis: clinical manifestations and implications for treatment journal February 2002
TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis journal December 2002
Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: A possible role in asthma? journal April 2004
CD40 and OX40 ligand are increased on stimulated asthmatic airway smooth muscle journal February 2005
Antagonism of Airway Tolerance by Endotoxin/Lipopolysaccharide through Promoting OX40L and Suppressing Antigen-Specific Foxp3 + T Regulatory Cells journal December 2008
Development of Allergic Inflammation in a Murine Model of Asthma Is Dependent on the Costimulatory Receptor Ox40 journal February 2001
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma journal March 2009
Chronic Cough Due to Nonasthmatic Eosinophilic Bronchitis journal January 2006
Randomized Controlled Trial of Oral Antifungal Treatment for Severe Asthma with Fungal Sensitization: The Fungal Asthma Sensitization Trial (FAST) Study journal January 2009
Inflammatory cell microlocalisation and airway dysfunction: cause and effect? journal August 2007

Cited By (6)

Targeting IL4/IL4R for the treatment of epithelial cancer metastasis journal September 2015
OX 40L blockade and allergen‐induced airway responses in subjects with mild asthma journal December 2013
Does airway smooth muscle express an inflammatory phenotype in asthma?: Airway smooth muscle and inflammation journal April 2011
OX40L induces helper T cell differentiation during cell immunity of asthma through PI3K/AKT and P38 MAPK signaling pathway journal March 2018
Lung damage and airway remodelling in severe asthma journal December 2011
Could OX40 agonist antibody promote activation of the anti-tumor immune response in gastric cancer? journal March 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ASM 5 airway smooth muscle
GINA 5
IL-4 receptor a
OX40 ligand
T helper 2
global initiative for asthma
interleukin
interquartile range
respiratory system
thymic stromal lymphopoietin