The IL-3/IL-5/GM-CSF common beta receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation

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dc.contributor.authorAsquith, K.
dc.contributor.authorRamshaw, H.
dc.contributor.authorHansbro, P.
dc.contributor.authorBeagley, K.
dc.contributor.authorLopez, A.
dc.contributor.authorFoster, P.
dc.date.issued2008
dc.descriptionCopyright © 2008 by The American Association of Immunologists, Inc.
dc.description.abstractThe eosinophil is a central effector cell in allergic asthma. Differentiation and function of eosinophils are regulated by the CD4 Th2 cytokines IL-3, IL-5, and GM-CSF, which all signal through a common beta receptor subunit (betac). Recent therapeutic approaches targeting IL-5 alone have not ablated tissue accumulation of eosinophils and have had limited effects on disease progression, suggesting important roles for IL-3 and GM-CSF. By using a mouse model of allergic airways inflammation, we show that allergen-induced expansion and accumulation of eosinophils in the lung are abolished in betac-deficient (betac-/-) mice. Moreover, betac deficiency resulted in inhibition of hallmark features of asthma, including airways hypersensitivity, mucus hypersecretion, and production of Ag-specific IgE. Surprisingly, we also identified a critical role for this receptor in regulating type 2 immunity. Th2 cells in the lung of allergen-challenged betac-/- mice were limited in their ability to proliferate, produce cytokines, and migrate to effector sites, which was attributed to reduced numbers of myeloid dendritic cells in the lung compartment. Thus, the betac plays a critical role in allergen-induced eosinophil expansion and infiltration and is pivotal in regulating molecules that promote both early and late phases of allergic inflammation, representing a novel target for therapy.
dc.description.statementofresponsibilityKelly L. Asquith, Hayley S. Ramshaw, Philip M. Hansbro, Kenneth W. Beagley, Angel F. Lopez and Paul S. Foster
dc.identifier.citationJournal of Immunology, 2008; 180(2):1199-1206
dc.identifier.doi10.4049/jimmunol.180.2.1199
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.orcidRamshaw, H. [0000-0001-9909-282X]
dc.identifier.orcidLopez, A. [0000-0001-7430-0135]
dc.identifier.urihttp://hdl.handle.net/2440/53591
dc.language.isoen
dc.publisherAmer Assoc Immunologists
dc.source.urihttp://www.jimmunol.org/cgi/content/abstract/180/2/1199
dc.subjectDendritic Cells
dc.subjectEosinophils
dc.subjectTh2 Cells
dc.subjectMacrophages, Alveolar
dc.subjectAnimals
dc.subjectMice
dc.subjectMice, Mutant Strains
dc.subjectAsthma
dc.subjectRespiratory Hypersensitivity
dc.subjectGranulocyte-Macrophage Colony-Stimulating Factor
dc.subjectInterleukin-3
dc.subjectInterleukin-5
dc.subjectAllergens
dc.subjectCytokines
dc.subjectLymphocyte Activation
dc.subjectSignal Transduction
dc.subjectCell Movement
dc.subjectCytokine Receptor Common beta Subunit
dc.titleThe IL-3/IL-5/GM-CSF common beta receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation
dc.typeJournal article
pubs.publication-statusPublished

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