Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal.
The receptors for IL-3, GM-CSF, and IL-5 share a common beta subunit (beta c), and mice have an additional IL-3 beta subunit (beta IL3). We have independently generated mice carrying null mutations of each molecule. beta c mutant bone marrow showed no response to GM-CSF or IL-5, whereas IL-3 stimulation of beta c or beta IL3 mutant bone marrow was normal. beta c mutant mice showed lung pathology consisting of lymphocytic infiltration and areas resembling alveolar proteinosis, and also exhibited low basal numbers of eosinophils. Infection of beta c mutant mice by Nippostrongylus brasiliensis resulted in the absence of blood and lung eosinophilia. Animals repopulated with beta c mutant bone marrow cells showed slower leukocyte recovery and reduced eosinophil numbers. These data define the role of beta c in vivo, and show a phenotype that is likely to be the cumulative effect of loss of GM-CSF and IL-5 stimulation.
Nishinakamura
R
R
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304-1104.
Nakayama
N
N
Hirabayashi
Y
Y
Inoue
T
T
Aud
D
D
McNeil
T
T
Azuma
S
S
Yoshida
S
S
Toyoda
Y
Y
Arai
K
K
D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology*; D005434:Flow Cytometry; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009559:Nippostrongylus / Q000276:immunology; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D018123:Receptors, Interleukin / Q000502:physiology; D016185:Receptors, Interleukin-3 / Q000502:physiology; D053649:Receptors, Interleukin-5; D017206:Strongylida Infections / Q000276:immunology
D018121:Receptors, Cytokine; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5