The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation.
- Publisher:
- AMER ASSOC IMMUNOLOGISTS
- Publication Type:
- Journal Article
- Citation:
- Journal of immunology (Baltimore, Md. : 1950), 2008, 180, (2), pp. 1199-1206
- Issue Date:
- 2008-01
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The Il-3:IL-5:GM-CSF common B receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation.pdf | Published version | 460.97 kB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Asquith, KL | |
dc.contributor.author | Ramshaw, HS | |
dc.contributor.author | Hansbro, PM | |
dc.contributor.author | Beagley, KW | |
dc.contributor.author | Lopez, AF | |
dc.contributor.author | Foster, PS | |
dc.date.accessioned | 2020-12-22T23:02:43Z | |
dc.date.available | 2020-12-22T23:02:43Z | |
dc.date.issued | 2008-01 | |
dc.identifier.citation | Journal of immunology (Baltimore, Md. : 1950), 2008, 180, (2), pp. 1199-1206 | |
dc.identifier.issn | 0022-1767 | |
dc.identifier.issn | 1550-6606 | |
dc.identifier.uri | http://hdl.handle.net/10453/144915 | |
dc.description.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. | |
dc.format | ||
dc.language | eng | |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | |
dc.relation.ispartof | Journal of immunology (Baltimore, Md. : 1950) | |
dc.relation.isbasedon | 10.4049/jimmunol.180.2.1199 | |
dc.rights | info:eu-repo/semantics/restrictedAccess | |
dc.subject | 1107 Immunology | |
dc.subject.classification | Immunology | |
dc.subject.mesh | Dendritic Cells | |
dc.subject.mesh | Eosinophils | |
dc.subject.mesh | Th2 Cells | |
dc.subject.mesh | Macrophages, Alveolar | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Mutant Strains | |
dc.subject.mesh | Asthma | |
dc.subject.mesh | Respiratory Hypersensitivity | |
dc.subject.mesh | Granulocyte-Macrophage Colony-Stimulating Factor | |
dc.subject.mesh | Interleukin-3 | |
dc.subject.mesh | Interleukin-5 | |
dc.subject.mesh | Allergens | |
dc.subject.mesh | Cytokines | |
dc.subject.mesh | Lymphocyte Activation | |
dc.subject.mesh | Signal Transduction | |
dc.subject.mesh | Cell Movement | |
dc.subject.mesh | Cytokine Receptor Common beta Subunit | |
dc.subject.mesh | Allergens | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Asthma | |
dc.subject.mesh | Cell Movement | |
dc.subject.mesh | Cytokine Receptor Common beta Subunit | |
dc.subject.mesh | Cytokines | |
dc.subject.mesh | Dendritic Cells | |
dc.subject.mesh | Eosinophils | |
dc.subject.mesh | Granulocyte-Macrophage Colony-Stimulating Factor | |
dc.subject.mesh | Interleukin-3 | |
dc.subject.mesh | Interleukin-5 | |
dc.subject.mesh | Lymphocyte Activation | |
dc.subject.mesh | Macrophages, Alveolar | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Mutant Strains | |
dc.subject.mesh | Respiratory Hypersensitivity | |
dc.subject.mesh | Signal Transduction | |
dc.subject.mesh | Th2 Cells | |
dc.title | The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. | |
dc.type | Journal Article | |
utslib.citation.volume | 180 | |
utslib.location.activity | United States | |
utslib.for | 1107 Immunology | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
utslib.copyright.status | closed_access | * |
dc.date.updated | 2020-12-22T23:02:33Z | |
pubs.issue | 2 | |
pubs.publication-status | Published | |
pubs.volume | 180 | |
utslib.citation.issue | 2 |
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.
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