The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation
Asquith, Kelly L., Ramshaw, Hayley S., Hansbro, Philip M., Beagley, Kenneth W., Lopez, Angel F., & Foster, Paul S. (2008) The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. Journal of Immunology, 180(2), pp. 1199-1206.
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.
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|Item Type:||Journal Article|
|Additional Information:||For more information, please refer to the journal's website (see hypertext link) or contact the author.|
|Keywords:||cells and tissue, infectious diseases, ihbi, beagley, Allergens, athma, immunology, Cytokine Receptor Common beta Subunit, Cytokines, Dendritic Cells, Eosinophils, Granulocyte, Macrophage Colony, Stimulating Factor, Interleukin, 3, Interleukin, 5, Lymphocyte Activation, Respiratory Hypersensitivity, Signal Transduction, Th2 Cells|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Microbiology not elsewhere classified (060599)|
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Metabolism (060104)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Infectious Agents (060502)
|Divisions:||Past > QUT Faculties & Divisions > Faculty of Science and Technology|
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2008 American Association of Immunologists|
|Deposited On:||10 Jun 2008|
|Last Modified:||11 Aug 2011 02:59|
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