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

UA Temann, P Ray, RA Flavell - The Journal of clinical …, 2002 - Am Soc Clin Investig
UA Temann, P Ray, RA Flavell
The Journal of clinical investigation, 2002Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation