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The IL‐3/IL‐5/GM‐CSF Common β Receptor Plays a Pivotal Role in Regulating Th2 Immunity and Allergic Airway Inflammation
Author(s) -
Asquith Kelly Lyn,
Ramshaw Hayley,
Lopez Angel,
Foster Paul Stephen
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.670.12
Subject(s) - immunology , eosinophil , allergic inflammation , inflammation , plasmacytoid dendritic cell , innate lymphoid cell , medicine , immunoglobulin e , interleukin 5 , dendritic cell , biology , immunity , cytokine , interleukin , asthma , immune system , antibody
The eosinophil is a central effector cell in allergic asthma. Differentiation and function of eosinophils is regulated by interleukin (IL)‐3, IL‐5 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), which all signal through a common β receptor subunit (βc). Recent therapeutic approaches targeting IL‐5 alone have had limited effects on disease progression. By employing mice lacking the βc and β IL‐3 receptor subunits we were able to interrupt signalling through all three eosinophilopoietic cytokines and prevent allergen‐induced expansion and accumulation of eosinophils in the lung in a mouse model of allergic airways inflammation. Moreover, βc deficiency resulted in inhibition of hallmark features of asthma including airways hypersensitivity, mucus hypersecretion and antigen‐specific IgE. Surprisingly, we also identified a critical role for the βc 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 subunit plays a critical role in allergen‐induced eosinophil responses and is pivotal in regulating molecules that promote both early and late phases of allergic inflammation, representing a novel target for therapy. (Supported by the NIH and NHMRC)