title: T(H)2 cytokines modulate the IL-9R expression on human neutrophils.
abstract: 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-9Ralpha in unfractionated and purified human neutrophils from atopic asthmatics, atopic non-asthmatics and healthy normal controls. We demonstrate that T(H)2 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-9Ralpha in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-kappaB did not affect T(H)2-mediated IL-9Ralpha expression in human neutrophils although IFN-gamma and IL-10 down-regulated IL-9Ralpha expression when co-incubated with IL-4, IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN-gamma and IL-10 on modulating the inducible IL-9Ralpha expression levels on peripheral blood neutrophils by T(H)2 cytokines.
authors.affiliation: Department of Immunology and the CIHR National Training Program in Allergy and Asthma, University of Manitoba, Winnipeg, Mannitoba, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dragon
authors.forename: Manrit Kaur
authors.initials: MK
authors.lastname: Takhar
authors.forename: Lianyu
authors.initials: L
authors.lastname: Shan
authors.forename: Kent T
authors.initials: KT
authors.lastname: Hayglass
authors.forename: F Estelle
authors.initials: FE
authors.lastname: Simons
authors.forename: Abdelilah S
authors.initials: AS
authors.lastname: Gounni
mesh_terms: D001249:Asthma / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D053651:Receptors, Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D053651:Receptors, Interleukin-9