Interleukin (IL)-9 is a T helper (Th) 2 cytokine recently implicated as an
essential factor in determining susceptibility to asthma. Transgenic mice o
verexpressing IL-9 exhibit many features that are characteristic of human a
sthma. To better understand the mechanism by which I L-9 mediates the vario
us biologic activities in asthma, we performed suppressive subtraction hybr
idization with whole lung from IL-9 transgenic and control mice. Here we re
port the identification of mCLCA3, a calcium-activated chloride channel tha
t was specifically induced in the lung epithelium of IL-9 transgenic mice.
Expression of mCLCA3 could also be induced by intratracheal administration
of IL-9 or other Th2 cytokines (IL-4, IL-13), but not by interferon-gamma.
Moreover, expression of mCLCA3 was induced in the lung of antigen-exposed m
ice, and this induction could be suppressed by neutralizing IL-9 antibody t
reatment, indicating IL-9 is both necessary and sufficient to induce mCLCA3
in this experimental model of asthma. Finally, we demonstrate that hCLCA1
is the human counterpart to mCLCA3 and is also induced in vitro in human pr
imary lung cells by Th2 cytokine treatment. Together, these data strongly i
mplicate the involvement of mCLCA3 (in mice) and hCLCA1 (in humans) in the
pathogenesis of Th2 cytokine-mediated asthmatic disorders.