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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Analysis of cytokine expression in total lung tissue. (a) Levels of vari...
Analysis of cytokine expression in total lung tissue. (a) Levels of various mRNAs encoding predominantly Th2 cytokines from individual IL-9 transgene-negative (lane 1, 2) and -positive (lane 3, 4) mice after transgene induction by doxycycline were compared by RPA. The P32-labeled multiprobe template set (T) was used as a size marker. Levels of L32 and GAPDH mRNAs encoding housekeeping genes were used to ensure equal loading of samples. (b) Levels of mRNA encoding IL-4 were evaluated by RT-PCR using total lung RNA isolated from transgene-negative (lane 1, 2) and -positive (lane 3, 4) mice 14 days after IL-9 transgene induction by doxycycline. Levels of mRNA encoding HPRT, a housekeeping gene, were used to demonstrate equal loading of samples. Fragment sizes of a molecular-weight marker are indicated in base pairs.