Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2.
Interleukin (IL)-13 has recently been shown to play important and unique roles in asthma, parasite immunity, and tumor recurrence. At least two distinct receptor components, IL-4 receptor (R)alpha and IL-13Ralpha1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Ralpha2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Ralpha2, mice deficient in IL-13Ralpha2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Ralpha2-/- mice despite the fact that serum IL-13 was absent and immune interferon gamma production increased compared with wild-type mice. IL-13Ralpha2-deficient mice display increased bone marrow macrophage progenitor frequency and decreased tissue macrophage nitric oxide and IL-12 production in response to lipopolysaccharide. These results are consistent with a phenotype of enhanced IL-13 responsiveness and demonstrate a role for endogenous IL-13 and IL-13Ralpha2 in regulating immune responses in wild-type mice.
Wood
Nancy
N
Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140, USA. ddonaldson@wyeth.com
Whitters
Matthew J
MJ
Jacobson
Bruce A
BA
Witek
JoAnn
J
Sypek
Joseph P
JP
Kasaian
Marion
M
Eppihimer
Michael J
MJ
Unger
Michelle
M
Tanaka
Takashi
T
Goldman
Samuel J
SJ
Collins
Mary
M
Donaldson
Debra D
DD
Grusby
Michael J
MJ
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018390:Gene Targeting; D007136:Immunoglobulins / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000276:immunology / Q000378:metabolism; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
C508183:Il13ra1 protein, mouse; D007136:Immunoglobulins; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma