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)α and IL-13Rα1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Rα2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Rα2, mice deficient in IL-13Rα2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Rα2−/− mice despite the fact that serum IL-13 was absent and immune interferon γ production increased compared with wild-type mice. IL-13Rα2–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-13Rα2 in regulating immune responses in wild-type mice.
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17 March 2003
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March 17 2003
Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2
Nancy Wood,
Nancy Wood
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Matthew J. Whitters,
Matthew J. Whitters
2Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140
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Bruce A. Jacobson,
Bruce A. Jacobson
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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JoAnn Witek,
JoAnn Witek
2Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140
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Joseph P. Sypek,
Joseph P. Sypek
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Marion Kasaian,
Marion Kasaian
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Michael J. Eppihimer,
Michael J. Eppihimer
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Michelle Unger,
Michelle Unger
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Takashi Tanaka,
Takashi Tanaka
3Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
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Samuel J. Goldman,
Samuel J. Goldman
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Mary Collins,
Mary Collins
2Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140
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Debra D. Donaldson,
Debra D. Donaldson
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
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Michael J. Grusby
Michael J. Grusby
3Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
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Nancy Wood
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Matthew J. Whitters
2Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140
Bruce A. Jacobson
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
JoAnn Witek
2Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140
Joseph P. Sypek
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Marion Kasaian
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Michael J. Eppihimer
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Michelle Unger
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Takashi Tanaka
3Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
Samuel J. Goldman
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Mary Collins
2Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140
Debra D. Donaldson
1Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140
Michael J. Grusby
3Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115
Address correspondence to Debra D. Donaldson, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140. Phone: 617-665-5549; Fax: 617-665-5584; E-mail: [email protected]
*
Abbreviations used in this paper: EMSA, electrophoretic mobility shift assay; MLF, murine lung fibroblasts; NO, nitric oxide; RPA, RNase protection assay; RPM, resident peritoneal macrophages; STAT, signal transducer and activator of transcription.
Received:
June 04 2002
Revision Received:
January 23 2003
Accepted:
January 23 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (6): 703–709.
Article history
Received:
June 04 2002
Revision Received:
January 23 2003
Accepted:
January 23 2003
Citation
Nancy Wood, Matthew J. Whitters, Bruce A. Jacobson, JoAnn Witek, Joseph P. Sypek, Marion Kasaian, Michael J. Eppihimer, Michelle Unger, Takashi Tanaka, Samuel J. Goldman, Mary Collins, Debra D. Donaldson, Michael J. Grusby; Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2 . J Exp Med 17 March 2003; 197 (6): 703–709. doi: https://doi.org/10.1084/jem.20020906
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