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 2

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Total cell counts from lung lavage fluid. IL-9 transgene-negative (TG–) ...
Total cell counts from lung lavage fluid. IL-9 transgene-negative (TG–) and -positive (TG+) mice, 6 weeks of age, were housed with or without doxycycline-supplemented food over a period of 14 days. At three different time points mice were sacrificed, subjected to lung lavage, and total cell numbers assessed. Data are expressed as mean ± SD of counts from four to five animals per group. Significant differences in cell numbers compared with that of transgene-negative and -positive mice that did not receive doxycycline are indicated by an asterisk.