Molecular Mechanisms in Allergy and Clinical Immunology
Role of IL-9 in the pathophysiology of allergic diseases☆,☆☆

https://doi.org/10.1067/mai.2001.114238Get rights and content

Abstract

Considerable evidence from both human and animal studies indicates that CD4+ cells are the predominant cell type involved in the regulation of airway inflammation through the expression of TH2-type cytokines. The effects of TH2-type cytokines, particularly IL-4 and IL-5, on inflammatory and structural cells in airways have been studied in great detail. They were shown to be important for inflammatory cell maturation, activation and proliferation, IgE production, chemokine expression, mucus secretion, and bronchial hyperresponsiveness. Recent work has shown the potential importance of another TH2-type cytokine, IL-9. The development of transgenic mice overexpressing IL-9 has suggested a key role for this cytokine in the development of the asthmatic phenotype, including eosinophilic inflammation, bronchial hyperresponsiveness, elevated IgE levels, and increased mucus secretion. IL-9 has been shown to act on many cell types involved in asthma, including T cells, B cells, mast cells, eosinophils, neutrophils, and epithelial cells, and thus might be important in the pathophysiology of allergic asthma. (J Allergy Clin Immunol 2001;107:575-82.)

Section snippets

IL-9

IL-9 is a member of the 4-helix bundle cytokine family, which includes cytokines, such as IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-15. Both human IL-9 and murine IL-9 consist of a 14-kd glycoprotein, the mature form of which is composed of 144 amino acids along with a signal sequence of 18 amino acids.2, 12, 13 The IL-9 protein contains a high proportion of cationic amino acid residues and 10 cysteines and has 4 N-linked glycosylation sites. The homology between human and murine IL-9 is 55%

T cells

Clinical studies, as well as murine models, have shown that T cells play a central role in asthma. In respect to the profile of cytokines, local TH2-type profile of cytokines, including IL-9, has been shown to be produced within the airways of asthmatic subjects.29, 30 The major cellular source of IL-9 is the T lymphocyte, notably that of the CD4+ TH2 subset,2, 31 which is consistent with in vivo data from asthmatic subjects.29 Strong expression of IL-9 was observed after the stimulation of

Regulatory role of IL-9 in inflammatory cells associated with allergic diseases

The regulatory role of IL-9 in inflammatory cells associated with allergic diseases is illustrated in Fig 1.

. Potential role of IL-9 during allergic inflammation in the airways. IL-9, a TH2 cytokine, has a pleiotropic activity on inflammatory and structural cells associated with asthma, such as mast cells, T cells, eosinophils, and epithelial cells. Within the lung, IL-9 is mainly produced by T cells and, to a lesser extent, granulocytes. The effect of IL-9 (yellow arrows) leads to various

Il-9 and asthma

The in vivo importance of IL-9 in the pathophysiology of asthma was first determined in animal models of airway inflammation. Nicolaides et al15 have described a close association between the IL9 gene and bronchial hyperresponsiveness (BHR).15 Moreover, lung protein IL-9 levels are highly correlated with levels of airway responsiveness in mice.15, 62 Furthermore, selective overexpression of the IL9 gene within the lungs of transgenic mice resulted in massive airway inflammation, with

Conclusion

These results demonstrate that IL-9 influences many aspects of the pathogenesis of asthma. Thus continued elucidation of the mechanisms of action of this cytokine, as well as its interactions with other pathways, will greatly enhance our understanding of inflammatory diseases, such as asthma. This may have important consequences in the field of asthma and allergy, and IL-9 should be considered as a novel therapeutic target for controlling the development of airway inflammation and

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    ☆

    Supported by the Medical Research Council of Canada and Magainin Pharmaceuticals Inc.

    ☆☆

    Reprint requests: Qutayba Hamid, MD, PhD, Meakins-Christie Laboratories, 3626 St Urbain St, Montreal, Quebec, Canada H2X 2P2.

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