Enhanced Interleukin (IL)-13 Responses in Mice Lacking IL-13 Receptor α 2

Author:

Wood Nancy1,Whitters Matthew J.2,Jacobson Bruce A.1,Witek JoAnn2,Sypek Joseph P.1,Kasaian Marion1,Eppihimer Michael J.1,Unger Michelle1,Tanaka Takashi3,Goldman Samuel J.1,Collins Mary2,Donaldson Debra D.1,Grusby Michael J.3

Affiliation:

1. Department of Respiratory Disease, Wyeth Research, Cambridge, MA 02140

2. Department of Musculoskeletal Sciences, Wyeth Research, Cambridge, MA 02140

3. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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