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Type: Journal article
Title: The IL-3/IL-5/GM-CSF common beta receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation
Author: Asquith, K.
Ramshaw, H.
Hansbro, P.
Beagley, K.
Lopez, A.
Foster, P.
Citation: Journal of Immunology, 2008; 180(2):1199-1206
Publisher: Amer Assoc Immunologists
Issue Date: 2008
ISSN: 0022-1767
Statement of
Kelly L. Asquith, Hayley S. Ramshaw, Philip M. Hansbro, Kenneth W. Beagley, Angel F. Lopez and Paul S. Foster
Abstract: The 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.
Keywords: Dendritic Cells
Th2 Cells
Macrophages, Alveolar
Mice, Mutant Strains
Respiratory Hypersensitivity
Granulocyte-Macrophage Colony-Stimulating Factor
Lymphocyte Activation
Signal Transduction
Cell Movement
Cytokine Receptor Common beta Subunit
Description: Copyright © 2008 by The American Association of Immunologists, Inc.
DOI: 10.4049/jimmunol.180.2.1199
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