title: Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways.
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.
authors.affiliation: Immunology, Tissue Growth, and Repair Biomarker Discovery, Genentech, South San Francisco, CA 94080, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Choy
authors.forename: Barmak
authors.initials: B
authors.lastname: Modrek
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Abbas
authors.forename: Sarah
authors.initials: S
authors.lastname: Kummerfeld
authors.forename: Hilary F
authors.initials: HF
authors.lastname: Clark
authors.forename: Lawren C
authors.initials: LC
authors.lastname: Wu
authors.forename: Grazyna
authors.initials: G
authors.lastname: Fedorowicz
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D001980:Bronchi / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016130:Immunophenotyping / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators