- Title
- The IL-3/IL-5/GM-CSF common β receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation
- Creator
- Asquith, Kelly L.; Ramshaw, Hayley S.; Hansbro, Philip M.; Beagley, Kenneth W.; Lopez, Angel F.; Foster, Paul S.
- Relation
- Journal of Immunology Vol. 180, Issue 2, p. 1199-1206
- Relation
- http://www.jimmunol.org/cgi/content/abstract/180/2/1199
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2008
- Description
- 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 β receptor subunit (βc). 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 βc-deficient (βc⁺/⁺) mice. Moreover, βc 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 βc⁺/⁺ 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 βc 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.
- Subject
- eosinophil; allergic sthma; IL-3; IL-5; GM-CSF; β receptors; Th2; immunity; inflammation; airway
- Identifier
- uon:5180
- Identifier
- http://hdl.handle.net/1959.13/43046
- Identifier
- ISSN:0022-1767
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