Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology
Ulla-Angela Temann, … , Prabir Ray, Richard A. Flavell
Ulla-Angela Temann, … , Prabir Ray, Richard A. Flavell
Published January 1, 2002
Citation Information: J Clin Invest. 2002;109(1):29-39. https://doi.org/10.1172/JCI13696.
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Article

Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology

Abstract

IL-9 is a pleiotropic cytokine with multiple functions on many cell types involved in the pathology of human asthma. The constitutive overexpression of IL-9 in the lungs of transgenic mice resulted in an asthma-like phenotype. To define the contribution of IL-9 to lung inflammation we generated transgenic mice in which lung-specific expression of the IL-9 transgene is inducible by doxycycline. Transgene induction resulted in lymphocytic and eosinophilic infiltration of the lung, airway epithelial cell hypertrophy with mucus production, and mast cell hyperplasia, similar to that seen in mice that constitutively expressed IL-9 in their lungs. Various cytokines, including IL-4, IL-5, and IL-13, were expressed in the lung in response to IL-9. Blockade of IL-4 or IL-5 following IL-9 induction reduced airway eosinophilia without affecting mucus production. In contrast, neutralization of IL-13 completely abolished both lung inflammation and mucus production. These findings suggest that pathologic changes in the lung require additional signals beyond IL-9, provided by IL-4, IL-5, and IL-13, to develop fully.

Authors

Ulla-Angela Temann, Prabir Ray, Richard A. Flavell

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Figure 8

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Histologic staining for mucin after cytokine blockade. Light micrographs...
Histologic staining for mucin after cytokine blockade. Light micrographs of lung sections stained with AB/PAS from IL-9 transgene-negative (a) or –positive (b–f) mice that were housed for 14 days with doxycycline-supplemented food. During the entire time of IL-9 transgene induction selected groups of animals received Ab’s: (c) control Ab’s, hIgG; (d) anti–IL-4; (e) sIL-13Rα-Fc; (f) anti–IL-4 and sIL-13Rα-Fc. Lung sections from transgene-positive mice that received anti–IL-4 Ab’s, control Ab’s, or no Ab’s showed strong positive (magenta) staining for mucin in airway epithelial cells (arrows) and accumulation of inflammatory cells near blood vessels and airways (b–d). Infiltration of lung tissue with inflammatory cells or positive staining for mucin was not observed in sections from transgene-positive mice that received sIL-13Rα-Fc alone (e), or in combination with anti–IL-4 (f), or in transgene-negative mice (a). Original magnification ×300.