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Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Feb 01; Vol. 186 (3), pp. 1861-9. Date of Electronic Publication: 2010 Dec 27. - Publication Year :
- 2011
-
Abstract
- Asthma is canonically thought of as a disorder of excessive Th2-driven inflammation in the airway, although recent studies have described heterogeneity with respect to asthma pathophysiology. We have previously described distinct phenotypes of asthma based on the presence or absence of a three-gene "Th2 signature" in bronchial epithelium, which differ in terms of eosinophilic inflammation, mucin composition, subepithelial fibrosis, and corticosteroid responsiveness. In the present analysis, we sought to describe Th2 inflammation in human asthmatic airways quantitatively with respect to known mediators of inflammation and intercellular communication. Using whole-genome microarray and quantitative real-time PCR analysis of endobronchial biopsies from 27 mild-to-moderate asthmatics and 13 healthy controls with associated clinical and demographic data, we found that asthmatic Th2 inflammation is expressed over a variable continuum, correlating significantly with local and systemic measures of allergy and eosinophilia. We evaluated a composite metric describing 79 coexpressed genes associated with Th2 inflammation against the biological space comprising cytokines, chemokines, and growth factors, identifying distinctive patterns of inflammatory mediators as well as Wnt, TGF-β, and platelet-derived growth factor family members. This integrated description of the factors regulating inflammation, cell migration, and tissue remodeling in asthmatic airways has important consequences for the pathophysiological and clinical impacts of emerging asthma therapeutics targeting Th2 inflammation.
- Subjects :
- Adult
Asthma pathology
Asthma physiopathology
Biopsy
Bronchi pathology
Bronchi physiopathology
Cell Communication genetics
Female
Gene Expression Regulation genetics
Humans
Hypersensitivity immunology
Hypersensitivity pathology
Hypersensitivity physiopathology
Immunophenotyping methods
Inflammation genetics
Inflammation immunology
Inflammation physiopathology
Inflammation Mediators metabolism
Inflammation Mediators physiology
Male
Middle Aged
Oligonucleotide Array Sequence Analysis methods
Respiratory Mucosa immunology
Respiratory Mucosa pathology
Respiratory Mucosa physiopathology
Th2 Cells metabolism
Young Adult
Asthma immunology
Bronchi immunology
Cell Communication immunology
Gene Expression Regulation immunology
Th2 Cells immunology
Th2 Cells pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 186
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21187436
- Full Text :
- https://doi.org/10.4049/jimmunol.1002568