IL-9 and its receptor in allergic and nonallergic lung disease: Increased expression in asthma

Ayako Shimbara, Pota Christodoulopoulos, Abdelilah Soussi-Gounni, Ronald Olivenstein, Yutaka Nakamura, Roy C. Levitt, Nicholas C. Nicolaides, Kenneth J. Holroyd, Anne Tsicopoulos, Jean Jacques Lafitte, Benoit Wallaert, Qutayba A. Hamid

Research output: Contribution to journalArticlepeer-review

217 Scopus citations

Abstract

Background: Bronchial asthma is a chronic inflammatory disease associated with genetic components. Recently IL-9 has been reported as a candidate gene for asthma and to be associated with bronchial hyperresponsiveness and elevated levels of total serum IgE. Objective: To investigate the contribution of IL-9 to the pathogenesis of asthma, we examined the expression of IL-9 and its receptor (IL-9R) in bronchial tissue from subjects with atopic asthma (n = 10), chronic bronchitis (n = 11), and sarcoidosis (n = 9) and from atopic (n = 7) and nonatopic (n = 10) healthy control subjects. Methods: Bronchial biopsy specimens were examined for the presence of IL-9 and IL-9R protein and messenger RNA (mRNA) by immunocytochemistry and in situ hybridization, respectively. To phenotype the cells expressing IL-9 in asthmatic tissue, combined in situ hybridization and immunocytochemistry was also performed. Results: There was a highly significant difference (P < .001) in the expression of IL-9 mRNA in asthmatic airways (20.6 ± 4.0 cells/mm of basement membrane) compared with chronic bronchitis (5.6 ± 4.4), sarcoidosis (2.5 ± 1.8), atopic control subjects (7.7 ± 2.2), and healthy control subjects (2.7 ± 2.3). The number of IL-9 immunoreactive cells was also greater in asthmatic patients compared with the other groups (P < .05). Although the level of IL-9R mRNA expression did not differ in any of the groups (P > .05), IL-9R immunoreactivity was significantly higher in asthmatic compared with control subjects. Furthermore, IL-9 mRNA expression levels were also significantly correlated with FEV1 (P < .05) and the airway responsiveness to methacholine producing a 20% fall in FEV1 (P < .01). The cells expressing IL-9 mRNA in asthmatic tissue were CD3+ lymphocytes (68%), major basic protein+ eosinophils (16%), and elastase+ neutrophils (8%). Conclusion: The results of this study demonstrate the potential of IL-9 to be a marker for atopic asthma and furthermore suggest an important role for this cytokine in the pathophysiologic mechanisms of this disease.

Original languageEnglish (US)
Pages (from-to)108-115
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume105
Issue number1 I
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Asthma
  • Atopy
  • IL-9
  • IL-9 receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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