Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 293; no. 3; pp. L730 - L739
• Main Authors: Johnson, Jill R, Swirski, Filip K, Gajewska, Beata U, Wiley, Ryan E, Fattouh, Ramzi, Pacitto, Stephanie R, Wong, Jonathan K, Stampfli, Martin R, Jordana, Manel
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2007
• Subjects: Adenoviridae; Administration, Intranasal; Allergens - administration & dosage; Allergens - immunology; Allergens - pharmacology; Allergies; Animals; Antigens, Dermatophagoides - administration & dosage; Antigens, Dermatophagoides - immunology; Antigens, Dermatophagoides - pharmacology; Asthma; Bronchial Hyperreactivity - pathology; Bronchial Provocation Tests; Bronchoalveolar Lavage; Cytokines - metabolism; Dermatophagoides pteronyssinus; Dermatophagoides pteronyssinus - immunology; Female; Genotype & phenotype; Immunoglobulins - blood; Immunology; Inflammation; Inflammatory diseases; Interleukin-4 - deficiency; Lung - drug effects; Lung - immunology; Lung - pathology; Lungs; Mice; Mice, Inbred BALB C; Mice, Knockout; Spleen - cytology; Transforming Growth Factor beta - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00056.2007

Department of Pathology and Molecular Medicine and Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada Submitted 12 February 2007 ; accepted in final form 18 June 2007 Asthma is a chronic airway inflammatory disease that encompasses three cardinal processes: T helper (Th) cell type 2 (Th2)-polarized inflammation, bronchial hyperreactivity, and airway wall remodeling. However, the link between the immune-inflammatory phenotype and the structural-functional phenotype remains to be fully defined. The objective of these studies was to evaluate the relationship between the immunologic nature of chronic airway inflammation and the development of abnormal airway structure and function in a mouse model of chronic asthma. Using IL-4-competent and IL-4-deficient mice, we created divergent immune-inflammatory responses to chronic aeroallergen challenge. Immune-inflammatory, structural, and physiological parameters of chronic allergic airway disease were evaluated in both strains of mice. Although both strains developed airway inflammation, the profiles of the immune-inflammatory responses were markedly different: IL-4-competent mice elicited a Th2-polarized response and IL-4-deficient mice developed a Th1-polarized response. Importantly, this chronic Th1-polarized immune response was not associated with airway remodeling or bronchial hyperresponsiveness. Transient reconstitution of IL-4 in IL-4-deficient mice via an airway gene transfer approach led to partial Th2 repolarization and increased bronchial hyperresponsiveness, along with full reconstitution of airway remodeling. These data show that distinct structural-functional phenotypes associated with chronic airway inflammation are strictly dependent on the nature of the immune-inflammatory response. allergy; inflammation; lung; Th1/Th2 cells Address for reprint requests and other correspondence: M. Jordana, Dept. of Pathology and Molecular Medicine, Michael G. DeGroote Centre for Learning and Discovery, Rm. 4087, McMaster Univ., 1200 Main St. West, Hamilton, ON, Canada L8N 3Z5 (e-mail: jordanam{at}mcmaster.ca )