TH2 cytokines modulate the IL-9R expression on human neutrophils

Interleukin (IL)-9 is associated with key pathological features of asthma such as airway hyperresponsiveness, bronchoconstriction and mucus production. Inflammatory responses mediated by IL-9 rely on the expression of the IL-9R which has been reported on lung epithelial cells, T lymphocytes and recently on airway granulocyte infiltrates. In this study, we assessed the regulatory and constitutive cell surface expression of the IL-9Rα in unfractionated and purified human neutrophils from atopic asthmatics, atopic non-asthmatics and healthy normal controls. We demonstrate that T_H2 cytokines (IL-4 or IL-13) and granulocyte macrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and cell surface expression levels of the IL-9Rα in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-κB did not affect T_H2-mediated IL-9Rα expression in human neutrophils although IFN-γ and IL-10 down-regulated IL-9Rα expression when co-incubated with IL-4, IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN-γ and IL-10 on modulating the inducible IL-9Rα expression levels on peripheral blood neutrophils by T_H2 cytokines.