Human Neutrophils Express the Interleukin-15 Receptor α Chain (IL-15Rα) but Not the IL-9Rα Component

Abstract

The interleukin-15 receptor (IL-15R) is composed of at least three chains, namely γ_c, IL-2Rβ, and the recently identified IL-15Rα, while the IL-9R complex consists of γ_cand a subunit designated IL-9Rα. Our previous work and that of others have shown that human neutrophils express γ_cand IL-2Rβ (two components shared with IL-2R) but not IL-2Rα and that IL-15 is a neutrophil agonist, whereas IL-2 is not. In this study, using flow cytometry with a specific anti-human IL-15Rα, we show for the first time that human neutrophils express surface IL-15Rα. Although we previously found that IL-15 is a neutrophil agonist, our present work shows that IL-15 does not trigger superoxide production nor cell spreading onto glass. In addition, we report that human neutrophils do not respond to IL-9 with respect to the functions/responses studied, namely, superoxide production, spreading onto glass, cell shape changes, phagocytosis, RNA synthesis, and apoptosis. Further, our results show that neutrophils do not express IL-9Rα as assessed by flow cytometry with a specific anti-human IL-9Rα antibody that stains the transfected cell line BW-h9R used as positive control. Finally, our results indicate that γ_cexpression was not modulated and remained stable for up to 24 h when neutrophils were stimulated with all currently known “γ_cusers,” namely, IL-2, IL-4, IL-7, IL-9, and IL-15. We conclude that human neutrophils express all IL-15R components on their surface, including IL-15Rα, that IL-15 activates human neutrophils (as the IL-4 neutrophil agonist) by a mechanism which does not involve upregulation of γ_ccell surface expression, and that IL-9 is not a neutrophil agonist as demonstrated by the inability to modulate the tested functions/responses that correlate with lack of the IL-9R component, namely, IL-9Rα.