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Production: Defining a Novel Role for IFN- in the Regulation of Allergic Airway Inflammation1
*
Sections of Pulmonary and Critical Care Medicine and
Immunobiology,
Department of Dermatology and
§
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520; and
¶
Pathology and Laboratory Medicine Service, Veterans Affairs Connecticut Health Care System, West Haven, CT 06516
Airway eosinophilia in asthma is dependent on cytokines secreted by
Th2 cells, including IL-5 and IL-4. In these studies we investigated
why the absence of IL-4 led to a reduction in airway, but not lung
tissue, eosinophils. Using adoptively transferred, in vitro-generated
TCR-transgenic Th2 cells deficient in IL-4, we show that this effect is
independent of IL-5 and Th2 cell generation. Airway eosinophilia was no
longer inhibited when IL-4-/- Th2 cells were transferred
into IFN-
R-/- mice, indicating that IFN- was
responsible for reducing airway eosinophils in the absence of IL-4.
Intranasal administration of IFN- to mice after IL-4+/+
Th2 cell transfer also caused a reduction in airway, but not lung
parenchymal, eosinophils. These studies show that IL-4 indirectly
promotes airway eosinophilia by suppressing the production of IFN-.
IFN- reduces airway eosinophils by engaging its receptor on
hemopoietic cells, possibly the eosinophil itself. These studies
capitalize on the complex counterregulatory effects of Th1 and Th2
cytokines in vivo and clarify how IL-4 influences lung eosinophilia. We
define a new regulatory role for IFN-, demonstrating that
eosinophilic inflammation is differentially regulated at distinct sites
within the respiratory tract.
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