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PMID: 21187436 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 186 ·No. 3 ·2011-02-01 ·Pages 1861-9

Choy DF, Modrek B, Abbas AR, Kummerfeld S, Clark HF, Wu LC, Fedorowicz G, Modrusan Z, Fahy JV, Woodruff PG, Arron JR

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.

MeSH Terms
Adult Asthma/immunology,pathology,physiopathology Biopsy Bronchi/immunology,pathology,physiopathology Cell Communication/genetics,immunology Female Gene Expression Regulation/genetics,immunology Humans Hypersensitivity/immunology,pathology,physiopathology Immunophenotyping/methods Inflammation/genetics,immunology,physiopathology Inflammation Mediators/metabolism,physiology Male Middle Aged Oligonucleotide Array Sequence Analysis/methods Respiratory Mucosa/immunology,pathology,physiopathology Th2 Cells/immunology,metabolism,pathology Young Adult
Chemicals
Inflammation Mediators
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Choy David F
Immunology, Tissue Growth, and Repair Biomarker Discovery, Genentech, South San Francisco, CA 94080, USA.
Modrek Barmak
Abbas Alexander R
Kummerfeld Sarah
Clark Hilary F
Wu Lawren C
Fedorowicz Grazyna
Modrusan Zora
Fahy John V
Woodruff Prescott G
Arron Joseph R
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.1002568
Published
2011-02-01
Epub
2010-00-27
Pages
1861-9
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3981556
Subset
IM
Grants
NHLBI NIH HHS · P50 HL056385 · United States
NHLBI NIH HHS · HL080414 · United States
NHLBI NIH HHS · HL56385 · United States
NCRR NIH HHS · K23 RR017002 · United States
NHLBI NIH HHS · HL66564 · United States
NHLBI NIH HHS · R01 HL080414 · United States
NHLBI NIH HHS · R01 HL095372 · United States
NHLBI NIH HHS · F32 HL009572 · United States
NCRR NIH HHS · RR17002 · United States
NHLBI NIH HHS · R01 HL066564 · United States
NHLBI NIH HHS · HL09572 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.1002568 PMC Full Text View journal details
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